Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hepatocyte Growth Factor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1997

Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes.

Endothelial cells are known to secrete various antiproliferative and vasodilating factors. Although injury of endothelial cells has been postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes, the mechanisms of endothelial injury in diabetes are not yet clarified. Therefore, it is important to know the effects of high glucose on the factors that may influence endothelial cell growth. A novel member of endothelium-specific growth factors, hepatocyte growth factor (HGF), is produced in vascular cells. To investigate the effects of high glucose on vascular cells, we examined 1) the effects of high glucose on endothelial cell and vascular smooth muscle cell (VSMC) growth and 2) the effects of high glucose on local HGF production in endothelial cell and VSMC. Treatment of human aortic endothelial cell with a high concentration of D-glucose, but not mannitol and L-glucose, resulted in a significant decrease in cell number. Interestingly, addition of recombinant HGF attenuated high D-glucose-induced endothelial cell death. Therefore, we measured local HGF secretion of endothelial cell. Importantly, local HGF production was significantly decreased by high D-glucose treatment. In contrast, high D-glucose treatment resulted in a significant increase in the number of human aortic VSMCs, whereas local HGF production was significantly decreased in accordance with increase in D-glucose concentration. No significant changes in numbers were observed in VSMC treated with high mannitol and L-glucose. We also studied the mechanisms of local HGF suppression by high D-glucose. High D-glucose treatment stimulated transforming growth factor-beta (TGF-beta) concentration in endothelial cell and VSMC. Decreased local vascular HGF production was abolished by addition of anti-TGF-beta antibody. As TGF-beta inhibited local HGF production in endothelial cell and VSMC, increased TGF-beta induced by high D-glucose may suppress local HGF production. This study demonstrated that high D-glucose induced endothelial cell death, stimulated VSMC growth, and decreased local HGF production through the stimulation of TGF-beta production both in endothelial cell and VSMC. Overall, decrease in a local endothelial stimulant, HGF, by high D-glucose may be a trigger of endothelial injury in diabetes, potentially resulting in the progression of atherosclerosis.

Animals↗
PubMed2000

Autocrine interactions of keratinocyte growth factor, hepatocyte growth factor, and kit-ligand in the regulation of normal ovarian surface epithelial cells.

Ovarian tumors are primarily derived from the layer of epithelium surrounding the ovary termed the ovarian surface epithelium (OSE). Although extensive research has focused on established ovarian tumors, relatively little is known about the normal biology of the OSE that gives rise to ovarian cancer. The local expression and actions of growth factors are likely involved in both normal and tumorigenic OSE biology. The current study investigates the expression and action of keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and kit-ligand (KL) in normal ovarian surface epithelium (OSE). The actions of various growth factors on KGF, HGF, and KL expression are examined. Observations indicate that freshly isolated normal OSE express the genes for KGF, HGF, and KL and expression is maintained in vitro. KGF messenger RNA expression in OSE was found to be stimulated by KGF and HGF, but not KL. HGF expression in OSE was found to be stimulated by KGF, HGF, and KL. KL expression in OSE was also found to be stimulated by KGF, HGF, and KL. Therefore, the various growth factors can regulate the mRNA expression of each other in OSE. Effects of growth factors on OSE growth were examined. KGF, HGF, and KL stimulated OSE growth to similar levels as the positive control epidermal growth factor. Observations suggest that KGF, HGF, and KL interact to promote OSE growth and growth factor expression. The ability of these growth factors to interact in a positive autocrine feedback loop is postulated to be important for normal OSE biology. Paracrine interactions with the adjacent stromal cells will also be a factor in OSE biology. Abnormal interactions of these growth factors may be involved in the onset and progression of ovarian cancer.

Animals↗
PubMed1997

Establishment of human peripheral lung epithelial cell lines (HPL1) retaining differentiated characteristics and responsiveness to epidermal growth factor, hepatocyte growth factor, and transforming growth factor beta1.

Novel human epithelial cell lines retaining characteristic features of normal peripheral airway cells were established by transfecting the SV40 large T antigen gene into primary in vitro outgrowths from normal peripheral lung specimens. These lines, designated as HPL1A to HPL1E, showed the polygonal shapes typical of epithelial cells and expressed cytokeratin in abundance. Ultrastructural examination revealed the presence of microvilli, multivesicular bodies, and multilamellar body-like structures that are characteristic of type II pneumocytes, but expression of CC1O transcripts, a highly specific marker for Clara cells, was also observed. Response to transforming growth factor beta, epidermal growth factor (EGF), and hepatocyte growth factor, all of which are thought to be important growth-regulatory molecules for cellular proliferation and developmental processes of peripheral lung, was apparent. In the HPL1A case, markedly altered cell morphology and cytoskeletal organization, potent inhibition of cell growth, and increased expression of an extracellular matrix protein were noted with transforming growth factor beta. Interestingly, both EGF and hepatocyte growth factor stimulated anchorage-dependent growth, whereas only EGF could sustain anchorage-independent proliferation. The HPL1 lines are, to our knowledge, the first series of stable epithelial lines of human peripheral lung to be described. They should be valuable for investigating various aspects of growth regulation and oncogenic processes, including the mechanisms of acquisition of anchorage independence and the interrelationships of genetic changes identified previously in lung cancers. In addition, the HPL1 lines may also prove useful for development of in vitro models for other human lung disorders as well as to elucidate the mechanisms of peripheral lung differentiation.

Aged↗
PubMed1994

Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells.

We sought to determine the effects of exogenous epidermal growth factor (EGF), heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF-alpha), single-chain precursor hepatocyte growth factor (SC-HGF), double-chain mature HGF (DC-HGF), and keratinocyte growth factor (KGF) on proliferation, motility, and differentiation of first passage cultures of human corneal epithelial cells in serum-free chemically defined medium. The effect of EGF, HB-EGF, TGF-alpha, SC-HGF, DC-HGF, KGF or combinations of the growth factors on proliferation was measured by counting cells present after 3 weeks of culture and by immunostaining for the cell-cycle-specific nuclear proliferation antigen Ki-67. The effect of the factors on epithelial cell motility was assessed by morphometric analysis of photographs of cells migrating from confluent islands of cells. The effect of growth factors on differentiation of epithelial cells were determined by immunostaining epithelial cell islands for the keratin K3 and by Western blotting for keratin K3. EGF, alone or in combination with KGF and SC-HGF, significantly stimulated motility of epithelial cells at the periphery of confluent islands of cells and induced an elongated cell morphology. TGF-alpha, HB-EGF and DC-HGF produced motility effects similar to EGF. There was diminished proliferation of the migrating cells in response to EGF, HB-EGF, TGF-alpha or DC-HGF, while non-migrating epithelial cells in the center of confluent islands continued to proliferate in response to the growth factors. EGF, HB-EGF, TGF alpha or DC-HGF inhibited expression of the differentiation-related marker keratin K3 in epithelial cells, both at the edge and at the center of the islands. KGF stimulated proliferation of corneal epithelial cells at low density and in confluent islands of cells. KGF did not affect expression of keratin K3 or migration of epithelial cells. SC-HGF had no effect on corneal epithelial cells. These results indicate that the effects of EGF, HB-EGF, TGF-alpha and DC-HGF on corneal epithelial cell proliferation, motility and differentiation vary from those of KGF and SC-HGF. EGF, HB-EGF, TGF-alpha and DC-HGF induced changes in epithelial cell morphology and motility in cells plated at low cell density or in cells located at the edge of a confluent island. Thus, these effects appear to be dependent on the extent of cell-cell contact. The inhibitory effect of EGF, HB-EGF, TGF-alpha or DC-HGF on corneal epithelial cell differentiation, however, is independent of cell density.(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Western↗
PubMed1998

Thecal cell-granulosa cell interactions involve a positive feedback loop among keratinocyte growth factor, hepatocyte growth factor, and Kit ligand during ovarian follicular development.

Interactions between mesenchymal-derived thecal cells and epithelial-derived granulosa cells are essential for follicular development in the ovary. These mesenchymal-epithelial cell interactions are in part mediated by keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and Kit ligand (KL). This study investigates the hypothesis that thecal cell-derived growth factors (e.g. KGF and HGF) regulate granulosa cell function, and granulosa cell-derived growth factors (e.g. KL) regulate thecal cell function. Gonadotropin regulation of this cell-cell interaction is also examined. Sensitive quantitative RT-PCR assays were used to analyze gene expression of KGF, HGF, and KL in the ovary. Thecal cell-derived KGF and HGF stimulated KL expression in bovine granulosa cells. Granulosa cell-derived KL stimulated KGF and HGF expression in bovine thecal cells. These results suggest that thecal and granulosa cells interact in a positive feedback loop mediated by KGF, HGF, and KL. Previous studies have suggested that gonadotropins (i.e. FSH and LH) regulate locally produced growth factor expression in the ovary. Treatment of bovine granulosa cells with FSH and hCG (a LH agonist) directly stimulated KL expression. The LH agonist hCG was also found to stimulate both KGF and HGF expression in thecal cells. The actions of gonadotropins on follicular development may in part be indirectly regulated by KL, KGF, and HGF expression. A novel positive feedback loop was identified between thecal cells and granulosa cells that is mediated by KL, KGF, and HGF. Thecal cell-derived KGF and HGF can stimulate granulosa cell-derived KL expression, and KL, in turn, can stimulate thecal cell-derived KGF and HGF expression. Combined observations support the hypothesis that mesenchymal-epithelial cell interactions between thecal and granulosa cells can play a significant role during ovarian follicular development and mediate gonadotropin actions.

Animals↗
PubMed2003

Insulin-like growth factors, hepatocyte growth factor and transforming growth factor-alpha in mouse tongue myogenesis.

Many reports have shown that tongue striated muscles have several unique characteristics not found in other skeletal muscles such as limb and trunk. Several peptide growth factors are reported to play important roles in skeletal myogenesis. In this article, the roles of insulin-like growth factors (IGF), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha in mouse tongue myogenesis were studied using an organ culture system of the mandible or tongue obtained from mouse embryos. It was found that IGF-I promotes the differentiation of tongue myoblasts. HGF plays an essential role in the migration and proliferation of tongue myogenic cells, and inhibits the differentiation of tongue myoblasts. TGF-alpha does not play an essential role in the proliferation of tongue myogenic cells, but does promote the early differentiation of tongue myoblasts. The role of IGF-I in the differentiation of tongue myoblasts, and that of HGF in the migration, proliferation and differentiation of tongue myogenic cells appear to be almost identical to their roles in the myogenesis of limb and cultured myogenic cell lines. However, the role of TGF-alpha in the proliferation and differentiation of tongue myogenic cells appears to be different from its role in the myogenesis of limb and cultured myogenic cell lines such as C2 and L6.

Animals↗
PubMedDate not supplied

Serum evaluation of angiogenic cytokine basic fibroblast growth factor, hepatocyte growth factor and TNF-alpha in patients with myelodysplastic syndromes: correlation with bone marrow microvascular density.

Recent studies have documented that angiogenesis plays a significant role in haematological malignancies, including mylodysplastic syndromes (MDS). Basic fibroblast growth factor (b-FGF), Hepatocyte growth factor (HGF) and Tumor necrosis factor-alpha (TNF-alpha) are multifunctional cytokines that potently stimulate angiogenesis. The aim of the present study was to evaluate the microvascular density (MVD) and the serum levels of these angiogenic factors in patients with myelodysplastic syndromes (MDS). In 61 patients with MDS, MVD was measured in bone marrow biopsies and b-FGF, HGF and TNF-alpha were determined in the serum of the same patients by enzyme-linked immunosorbent assay (ELISA). Serum levels of b-FGF, HGF and TNF-alpha as well as MVD in the bone marrow were increased in MDS patients compared to healthy controls (p<0.0001). Levels of b-FGF, HGF and TNF-alpha were also significantly higher in high-risk for leukemic transformation MDS than in low-risk (p<0.0001). Significant differences were also found regarding MVD in high and low risk patients (p<0.001). Both b-FGF and HGF levels were significant predictors of survival (p<0.0005, log-rank test). The present study showed that serum levels of b-FGF, HGF and TNF-alpha are significantly increased and dependent on the severity of MDS suggesting that the determination of these parameters may offer considerable information regarding disease progression and prognosis.

Aged↗
PubMed2000

Vascular endothelial growth factor, hepatocyte growth factor/scatter factor, basic fibroblast growth factor, and placenta growth factor in human meningiomas and their relation to angiogenesis and malignancy.

OBJECTIVE: Angiogenesis is mediated by a number of different growth factors and appears vital for tumor growth. The understanding of angiogenic mechanisms could offer new therapeutic perspectives; in this context, the role of four potentially angiogenic growth factors was analyzed in a large series of meningiomas of different grades. METHODS: Vascular endothelial growth factor (VEGF), placenta growth factor, hepatocyte growth factor/scatter factor, and basic fibroblast growth factor were quantified in 69 tumors by enzyme-linked immunosorbent assay. Microvessel density and proliferative activity were determined on paraffin sections, and clinical tumor invasiveness was rated. Induction of endothelial chemotaxis and capillary-like tube formation were studied in vitro using modified Boyden chamber assays and three-dimensional collagen gel assays, respectively. RESULTS: Tumors included 40 benign (World Health Organization [WHO] Grade I), 21 atypical (WHO Grade II), and 8 anaplastic/malignant (WHO Grade III) meningiomas. We found a correlation between meningioma grade and VEGF content (r = 0.37, P = 0.002), which was 2-fold higher in atypical than in benign meningiomas (P = 0.022) and 10-fold higher in malignant than in benign meningiomas (P = 0.025). Among different subtypes of Grade I meningiomas, VEGF levels were 10-fold higher in meningothelial than in fibrous meningiomas (P = 0.015). None of the other three factors investigated showed any association with tumor grade, microvessel density, or invasiveness, and VEGF also did not correlate with vascularity or invasiveness. Moreover, vascularity did not increase with malignancy grade. Endothelial chemotaxis and capillary-like tube formation in vitro were induced by meningioma extracts and were most effectively blocked by co-addition of antibodies against basic fibroblast growth factor, followed by anti-VEGF, whereas anti-hepatocyte growth factor/scatter factor was not effective. The chemotactic activity of meningioma extracts on endothelial cells correlated with their VEGF content (r = 0.6, P = 0.003). CONCLUSION: Meningiomas do not show an angiogenic switch involving VEGF and/or hepatocyte growth factor/scatter factor, as has previously been found in gliomas. Nevertheless, the biological activity of VEGF and basic fibroblast growth factor in meningiomas suggests that both are potential targets for antiangiogenic therapy in meningiomas of all WHO grades.

Chemotaxis↗
PubMed1999

Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis.

Angiogenesis is a possible target in the treatment of human gliomas. To evaluate the role of 3 growth factors, vascular endothelial growth factor (VEGF), hepatocyte growth factor/scatter factor (HGF/SF) and basic fibroblast growth factor (bFGF), in the angiogenic cascade, we determined their levels in extracts of 71 gliomas by enzyme-linked immunosorbent assay (ELISA). The levels of bFGF were only marginally different between gliomas of World Health Organization (WHO) grade II (low grade) and grades III and IV (high grade). In contrast, the mean concentrations of VEGF were 11-fold higher in high-grade tumors and those of HGF/SF 7-fold, respectively. Both were highly significantly correlated with microvessel density (p < 0.001) as determined by immunostaining for factor VIII-related antigen. In addition, VEGF and HGF/SF appeared to be independent predictive parameters for glioma microvessel density as determined by multiple regression analysis. We measured the capacity of all 3 factors to induce endothelial tube formation in a collagen gel. In this assay, bFGF was found to be an essential cofactor with which VEGF as well as HGF/SF were able to synergize independently. According to the concentrations of angiogenic factors, extracts from high-grade tumors were significantly more potent in the tube formation assay than the low-grade extracts (p = 0.02). Adding neutralizing antibodies to bFGF, VEGF and HGF/SF together with the extracts, tube formation was inhibited by up to 98%, 62% and 54%, respectively. Our findings suggest that bFGF is an essential cofactor for angiogenesis in gliomas, but in itself is insufficient as it is present already in the sparsely vascularized low-grade tumors. Upon induction of angiogenesis in high-grade tumors, bFGF may synergize with rising levels of not only VEGF but possibly also with HGF/SF, which appears here to be an independent angiogenic factor.

Cells, Cultured↗
PubMed1993

Increased gene expression of scatter factor-hepatocyte growth factor and basic fibroblast growth factor in granulation tissue in the rat.

Scatter factor-hepatocyte growth factor is a protein secreted by fibroblasts which disperses colonies of epithelial cells and keratinocytes in culture. The factor is also a patent mitogen for hepatocytes, synthesized in the liver. Basic fibroblast growth factor, another heparin-binding factor, is most abundant in the brain but also plays a role in wound healing. Using a solution hybridization/RNAase protection assay, we have measured the abundance of messenger RNA for scatter factor-hepatocyte growth factor and basic fibroblast growth factor in granulation tissue obtained from subcutaneously Hunt-Schilling wound cylinders. The levels of scatter factor-hepatocyte growth factor messenger RNA increased after weeks 2 through 4 to a twofold higher level in weeks 5 through 7 after implantation of the cylinders, whereas no changes in basic fibroblast growth factor messenger RNA levels were noticed. At week 3 after implantation of the cylinders, scatter factor-hepatocyte growth factor messenger RNA levels in granulation tissue were more than threefold higher than in skin dermis fibroblasts but markedly lower than in the liver. The abundance of basic fibroblast growth factor messenger RNA was also significantly increased in granulation tissue compared with dermis but, as expected, markedly lower than in the brain. In conclusion, the gene expression of the scatter factor-hepatocyte growth factor, as well as basic fibroblast growth factor, is increased in granulation tissue. Because there was a time-dependent increase in the expression of scatter factor-hepatocyte growth factor, it is hypothesized that scatter factor-hepatocyte growth factor acts as a signal from fully developed granulation tissue to stimulate skin epithelial cells to scatter over the wound.

Journal Article↗
PubMed1996

Hepatocyte growth factor and hepatocyte growth factor receptor in the lacrimal gland, tears, and cornea.

PURPOSE: The purpose of this study was to characterize the expression of hepatocyte growth factor (HGF) and HGF receptor proteins in lacrimal gland, tears, and cornea. METHODS: The reverse transcription-polymerase chain reaction method was used to detect HGF and HGF receptor messenger RNA in human lacrimal gland tissue. HGF and HGF (c-met) receptor monoclonal antibody specificity was demonstrated with fluorescent antibody sorting of cells engineered to express HGF or HGF receptor compared with control cell lines, enzyme-linked immunoadsorbent assay (ELISA), immunoprecipitation, and immunohistology with preabsorption. Immunohistochemistry was applied to study the distribution of HGF and HGF receptor expression in rabbit lacrimal gland tissue and in wounded and unwounded rabbit cornea. An ELISA was used to detect HGF in pooled samples of human tears and individual aliquots of tears collected from patients 1 day after anterior segment surgery. RESULTS: Amplification products of the expected size for HGF and HGF receptor mRNAs were detected in lacrimal tissue and were confirmed to be specific by hot blotting and nucleic acid sequencing. Hepatocyte growth factor protein was detected in interalveolar and interlobular connective tissue cells adjacent to glandular alveolar (acinar) cells and associated with the cells lining the interlobular ducts. Hepatocyte growth factor receptor protein was expressed in the glandular alveolar and interlobular ductal cells in the lacrimal gland and all three cell types of the cornea. It was detected in keratocyte and endothelial cells, and expression was increased in keratocytes after epithelial wounding. Hepatocyte growth factor was not present in corneal epithelial cells, but in the unwounded cornea a strong signal was associated with the epithelial cell surface. It was detected by ELISA in pooled normal tears at levels 186 to 290 pg/ml and in individual postoperative tear samples at 453 to 619 pg/ml. In some tear samples, HGF levels were below the sensitivity of the assay (97.5 pg/ml). CONCLUSIONS: The distribution of HGF receptor protein expression in the lacrimal gland suggests that HGF secreted by interalveolar connective tissue cells traverses the acinar cells and modulates functions in acinar and ductal epithelial cells. Hepatocyte growth factor likely collects within the interlobular ducts and becomes a component in normal tears. Thus, lacrimal gland HGF probably modulates corneal epithelial cell proliferation, motility, and differentiation. Its expression in keratocytes is upregulated after corneal epithelial wounding and probably contributes to the epithelial wound healing process.

Animals↗
PubMed1997

Astroglial expression of hepatocyte growth factor and hepatocyte growth factor activator in human brain tissues.

Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some other cells in various organs. A HGF activating protease, HGF activator (HGFA) has recently been identified as a key enzyme that regulates the activity of HGF in vivo. HGFA appears to be associated with the cell surface. We examined HGFA immunolabelling in the brains of neurologically normal and Alzheimer disease (AD) cases. Furthermore, we identified the expression of the mRNA for HGF and HGFA by in situ hybridization histochemistry. The HGFA antibody stained only astrocytes in the white matter in all the brain tissues. Expression of the mRNAs of HGF and HGFA was also seen in white matter astrocytes. These results suggest that, in human brain, secreted pro-HGF from astrocytes might be activated by HGFA on/or near the astrocytic cell surface.

Aged↗
PubMed1991

Effect of 2% dimethyl sulfoxide on the mitogenic properties of epidermal growth factor and hepatocyte growth factor in primary hepatocyte culture.

Two percent dimethyl sulfoxide (DMSO) reversibly inhibited DNA synthesis in primary rat hepatocyte cultures maintained with epidermal growth factor (EGF) or hepatocyte growth factor (HGF). These data suggest that, in vitro, DMSO is a non-specific inhibitor of hepatocyte proliferation, regardless of the stimulating mitogen. In addition, removal of DMSO from mitogen-free cultures resulted in an increase in DNA synthesis. Protein synthesis gradually but irreversibly declined in all cultures after DMSO removal. The relevance of these findings to regulation of hepatocyte growth is discussed.

Animals↗
PubMed1994

Induction of hepatocyte growth factor in human skin fibroblasts by epidermal growth factor, platelet-derived growth factor and fibroblast growth factor.

Hepatocyte growth factor (HGF) is a potent mitogen for rat and human hepatocytes in primary culture and appears to be the physiological hepatotrophic factor that triggers or modulates liver regeneration. Regulation of HGF gene expression and the protein production in human skin fibroblasts was examined. Addition of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF) and transforming growth factor-alpha (TGF-alpha) to confluent cultures of the cells markedly stimulated HGF secretion from the cells. The stimulating effect of EGF, PDGF and bFGF was further investigated. The effect of all three growth factors was maximal at 3-30 ng/ml and was accompanied by an increase in HGF mRNA levels. The mRNA levels were not elevated at 5 h but were at 10 h or more after addition of EGF. The levels of HGF mRNA in fibroblasts treated with the optimal doses of EGF, PDGF, bFGF, aFGF and TGF-alpha for 24 h were 6, 4, 5, 4 and 5 times that of control cultures incubated in medium only, respectively. The growth factor-induced HGF mRNA expression and HGF secretion was inhibited by addition of TGF-beta 1 or dexamethasone. Pretreatment with a high dose of phorbol 12-myristate 13-acetate (PMA), which causes down-regulation in protein kinase C (PKC) activity and PMA-induced HGF secretion, did not reduce the effects of the growth factors on HGF mRNA expression and HGF secretion, but rather enhanced them.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1991

Structure and function of hepatocyte growth factor.

Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes in primary culture, was first found in sera of partial hepatectomized rats and seems to be a hepatotrophic factor for liver regeneration which has not been purified over the past 30 years. HGF is composed of the 69 kDa alpha-subunit and the 34 kDa beta-subunit. Molecular cloning reveals that HGF is derived from a single chain precursor of 728 amino acid residues and it contains 4 kringle domains in the alpha-subunit. HGF gene spans about 70kb and consists of 18 exons and 17 introns. HGF is now thought to be a pleiotropic factor influencing a cell growth and cell motility for various epithelial cells. HGF receptor with Kd = 20-30pm is widely distributed in various epithelial cells including hepatocytes. HGF mRNA and HGF activity increase markedly in liver after various liver injuries and in kidney following unilateral nephrectomy or acute renal injury. Moreover, HGF mRNA is induced even in the intact lung in response to liver and kidney injury. In situ hybridization reveals that HGF-producing cells are mesenchymal cells such as Kupffer cells and sinusoidal endothelial cells in liver, fenestrated endothelial cells in kidney, and macrophages and endothelial cells in lung. Thus, HGF may play an important role as a paracrine or endocrine mediator through an epithelial-mesenchymal interaction in wound-healing, tissue or organ regeneration, morphogenesis and carcinogenesis.

Amino Acid Sequence↗
PubMed1997

Effect of transforming growth factor-beta1 and -beta2 on in vitro rabbit corneal epithelial cell proliferation promoted by epidermal growth factor, keratinocyte growth factor, or hepatocyte growth factor.

Corneal epithelial wound healing is intimately controlled by a variety of growth factors, such as epidermal growth factor (EGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and transforming growth factor-betas (TGF-betas). In this study, we investigate the effects of TGF-beta1 and TGF-beta2 on cultured rabbit corneal epithelial cell proliferation promoted by EGF, KGF, or HGF. Both TGF-beta1 and -beta2 dose-dependently inhibited corneal epithelial cell proliferation promoted by KGF (40 ng ml-1) and HGF (40 ng ml-1), and weakly inhibited cell proliferation promoted by EGF (4 ng ml-1). Furthermore, the inhibitory effect tended to be stronger with TGF-beta2 than TGF-beta1. These findings suggest that TGF-beta1 and -beta2 play important roles as negative modulators against the cell proliferation effect of EGF, KGF and HGF.

Animals↗
PubMed1989

Molecular cloning and expression of human hepatocyte growth factor.

Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. The partial purification and characterization of HGF have been reported. We have demonstrated that pure HGF from rat platelets is a new growth factor effective at concentrations as low as 1 ng ml-1. The effects of HGF and epidermal growth factor (EGF) are additive. The activity of HGF is not species-specific, although it does not stimulate growth in Swiss 3T3 fibroblasts. HGF has a relative molecular mass (Mr) of 82,000 and is a heterodimer composed of a large alpha-subunit of Mr 69,000 and a small beta-subunit of Mr 34,000. Here we report the amino-acid sequence of human HGF determined by complementary DNA cloning and the expression of biologically active human HGF from COS-1 cells transfected with cloned cDNA. The nucleotide sequence of the human HGF cDNA reveals that both alpha- and beta-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids.

Amino Acid Sequence↗
PubMedDate not supplied

[Physiologic and physiopathologic role of hepatocyte growth factor].

Hepatocyte growth factor (HGF), originally described as an hepatocyte specific mitogen, has been shown to be a potent stimulator of DNA synthesis in a wide variety of cell types. In addition to its mitogenic effect, HGF has the unique ability to transmit information that determines the spatial organization of epithelial cells in tissues as well as induce cell migration and invasion of extracellular matrix in a variety of epithelial cells. HGF is involved in physiological processes like embryogenesis and development, and also in pathophysiological process as regeneration and carcinogenesis. Although the role that HGF plays in liver cancer is not clear, the findings strongly suggest that it influences the malignant cells. The present paper shows a review on the advances in the knowledge of HGF in physiological processes and in those related to liver diseases.

Extracellular Matrix↗