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PubMed2003

FGF signaling inhibits the proliferation of human myeloma cells and reduces c-myc expression.

BACKGROUND: Multiple myeloma is a cancer of antibody producing plasma cells whose etiology is unknown. FGF signaling has been implicated in myeloma pathogenesis but its precise role remains unclear. RESULTS: Here, we investigate the biochemical and phenotypic consequences of FGF stimulation in several different human myeloma cell lines. We find that FGF signaling inhibits cell cycle progression in two lines and surprisingly, reduces the expression of c-myc while turning on c-fos. In several other lines, FGF signaling does not affect proliferation rate, including cells harboring translocated FGF Receptor 3. When cells are presented with a growth arrest signal, FGF addition induces cell death. CONCLUSIONS: By showing that FGF signaling inhibits mitogenesis and induces apoptosis, we demonstrate novel effects of activating this ubiquitous signaling pathway in multiple myeloma.

Apoptosis↗
PubMed2006

Zebrafish endoderm formation is regulated by combinatorial Nodal, FGF and BMP signalling.

In the zebrafish embryo, the mesoderm and endoderm originate from common precursors and segregate during gastrulation by mechanisms that are largely unknown. Understanding how the signalling pathways that regulate endoderm and mesoderm formation interact is crucial to understanding how the germ layers are established. Here, we have analysed how the FGF and BMP pathways interact with Nodal signalling during the process of endoderm formation. We found that activation of the FGF/ERK pathway disrupts endoderm formation in the embryo and antagonizes the ability of an activated form of Tar/Acvr1b to induce endoderm at the animal pole. By contrast, inhibition of FGF signalling increases the number of endodermal precursors and potentiates the ability of Tar*/Acvr1b to induce endoderm at the animal pole. Using a pharmacological inhibitor of the FGF receptor, we show that reducing FGF signalling partially rescues the deficit of endoderm precursors in bon mutant embryos. Furthermore, we found that overexpression of BMPs compromises endoderm formation, suggesting that formation of endoderm precursors is negatively regulated by BMPs on the ventral side. We show that simultaneous inhibition of the FGF/Ras and BMP pathways results in a dramatic increase in the number of endoderm precursors. Taken together, these data strongly suggest that BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling. Finally, we investigated the molecular basis for the FGF-MAPK-dependent repression of endoderm formation. We found that FGF/ERK signalling causes phosphorylation of Casanova/Sox32, an important regulator of endoderm determination, and provide evidence that this phosphorylation attenuates its ability to induce sox17. These results identify a molecular mechanism whereby FGF attenuates Nodal-induced endodermal transcription factors and highlight a potential mechanism whereby mesoderm and endoderm fates could segregate from each other.

Activin Receptors, Type I↗
PubMed1995

Multiple roles for FGF-3 during cranial neural development in the chicken.

FGF-3 has been implicated in the development of the hindbrain and otocyst in vertebrate embryos. Since the chicken embryo offers a favourable system in which to study the development of these structures, we have isolated and characterised cDNAs for chicken Fgf-3 and determined its pattern of expression in chick embryos from stage 3 (primitive streak) to stage 25 (early organogenesis). Within the developing cranial neural tube, Fgf-3 exhibits dynamic spatial and temporal expression. During extension of the head process, RNA is detected in the midline of the developing neural plate. In neurulating embryos, transcripts are observed initially in rhombomeres 4 and 5 of the hindbrain and later, in rhombomere 6. During hindbrain development, expression is lost from these rhombomeres, but becomes restricted to rhombomere boundaries, providing an intracellular marker which distinguishes a population of cells within boundary regions. Fgf-3 expression is elevated in ventral and medial boundary regions and is greatly reduced in dorsal parts. Studies of regenerating rhombomere boundaries show that Fgf-3 expression is induced in reforming boundaries when even-numbered rhombomere tissue is grafted next to odd, but not when like is juxtaposed to like. Fgf-3 disappears from boundary regions just prior to the loss of the morphological boundaries suggesting a boundary-associated function. Other sites of expression have also been identified. At early stages of development Fgf-3 is expressed in the epiblast and mesendoderm of the primitive streak, in mesoderm lateral to the streak and in Hensen's node. In older embryos transcripts are detected in the endoderm of the pharyngeal pouches, the ectoderm of the second and third pharyngeal arches and the stomodeum. Expression was also detected in the segmental plate and in the posterior half of the three most-recently generated somites.

Amino Acid Sequence↗
PubMed1997

A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula.

Signals released from Spemann's organizer, together with ventralizing factors such as BMPs, are necessary to pattern the dorsoventral axis of the vertebrate embryo. We report that a member of the FGF family, fgf-8, not secreted by the axial mesoderm but expressed in a dorsoventral gradient at the margin of the zebrafish gastrula, also contributes to the establishment of the dorsoventral axis of the embryo. Ectopic expression of FGF-8 leads to the expansion of dorsolateral derivatives at the expense of ventral and posterior domains. Moreover, FGF-8 displays some organizer properties as it induces the formation of a partial secondary axis in the absence of factors released from Spemann's organizer territory. Analysis of its interaction with the ventralizing factors, BMPs, reveals that overexpression of FGF-8 inhibits the expression of these factors in the ventral part of the embryo as early as blastula stage, suggesting that FGF-8 acts upstream of BMP2 and BMP4. We conclude that FGF-8 is involved in defining dorsoventral identity and is an important organizing factor responsible for specification of mesodermal and ectodermal dorsolateral territories of the zebrafish gastrula.

Amino Acid Sequence↗
PubMed1999

FGF-7 modulates ureteric bud growth and nephron number in the developing kidney.

The importance of proportioning kidney size to body volume was established by clinical studies which demonstrated that in-born defecits of nephron number predispose the kidney to disease. As the kidney develops, the expanding ureteric bud or renal collecting system induces surrounding metanephric mesenchyme to proliferate and differentiate into nephrons. Thus, it is likely that nephron number is related to ureteric bud growth. The expression patterns of mRNAs encoding Fibroblast Growth Factor-7 (FGF-7) and its high affinity receptor suggested that FGF-7 signaling may play a role in regulating ureteric bud growth. To test this hypothesis we examined kidneys from FGF-7-null and wild-type mice. Results of these studies demonstrate that the developing ureteric bud and mature collecting system of FGF-7-null kidneys is markedly smaller than wild type. Furthermore, morphometric analyses indicate that mature FGF-7-null kidneys have 30+/-6% fewer nephrons than wild-type kidneys. In vitro experiments demonstrate that elevated levels of FGF-7 augment ureteric bud growth and increase the number of nephrons that form in rodent metanephric kidney organ cultures. Collectively, these results demonstrate that FGF-7 levels modulate the extent of ureteric bud growth during development and the number of nephrons that eventually form in the kidney.

Animals↗
PubMed2006

Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail.

Members of the fibroblast growth factor family bind to one or more of the four closely related membrane-spanning FGF receptors. In addition to signaling through the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have studied the ability of the four FGF receptors to facilitate translocation of exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted from FGFR1 without abolishing translocation, whereas the C-terminal tail of the FGFRs, constituted by approximately 50 amino acids downstream of the kinase domain, plays a crucial role in FGF-1 translocation. Three amino acids residues within the C-terminal tail were found to be of particular importance for translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were sufficient to enable the receptor to support FGF-1 translocation. The results demonstrate a striking diversity in function of the four FGFRs determined by their C-terminal domain.

Amino Acid Sequence↗
PubMed1994

Acidic and basic FGF mRNA expression in the middle ear mucosa during experimental acute and chronic otitis media.

Fibroblast growth factors (FGFs) induce the proliferation and differentiation of cells of mesodermal and neuroectodermal origin. Using in situ hybridization, messenger ribonucleic acid encoding acidic FGF, basic FGF and FGF receptor 1 (FGFR1) were localized in the middle ear mucosa of experimental animals with acute and chronic immune-mediated otitis media with effusion (OME). Basic FGF-labeled cells were seen in the subepithelial connective tissue layer (SE) preferentially near the epithelial basement membrane. Acidic FGF-labeled cells were seen in the SE, preferentially near blood vessels and occasionally in the cellular middle ear effusion (CE). FGFR1-labeled cells were seen in the SE and in the CE. The distribution of labeled cells in the middle ear suggests that basic FGF is produced by fibroblasts, acidic FGF is produced by leukocytes, and FGFR1 is produced by both fibroblasts and leukocytes. A role is proposed for these peptides in the proliferation and maintenance of the middle ear submucosa during otitis media.

Acute Disease↗
PubMed1998

Basic fibroblast growth factor (FGF-2) in mouse tooth morphogenesis.

This study describes the spatio-temporal expression of basic Fibroblast growth factor (FGF-2) during odontogenesis of mouse as revealed by immunohistology. Parasagittal sections of mouse embryo head (13-18 day of gestation) containing various stages of developing tooth were incubated with a polyclonal anti-FGF-2 antibody and positive binding was evidentiated by using Streptavidin-Biotin complex-HRP system and AEC staining. We observed no FGF-2 staining at the dental lamina stage. At the bud stage slight staining is seen, limited to some epithelial cells. The intensity of the staining increases at the cap stage. In the bell stage, the stellate reticulum cells stain intensely. Later, odontoblasts and the dentin matrix stain deeply; but the epithelial cells stain faint. The extra cellular matrix of the dentin and dental papilla stain very intense but the enamel matrix is found negative. These results indicate the participation of FGF-2 in differentiation rather than in proliferation of tooth-forming cells. In particular, it appears that FGF-2 participates in odontoblast differentiation and in dentin matrix deposition. The spatio-temporally specific distribution pattern of FGF-2 in developing mouse tooth reported here emphasizes the importance of FGF-2 in mammalian odontogenesis.

Animals↗
PubMed1999

Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation.

Recently several chromosomal translocations involved in myeloma cases and myeloma cell lines; i.e., t(11;14)(q13;q32), t('8;14)(q24;q32), t(4;14)(q16.3;q32.3), t(6;14)(p25;q32), and t(14;16)(q32.3;q23), have been identified. These translocations are considered to dysregulate genes which may be concerned with myelomagenesis; i.e., PRAD1/cyclin D1, the c-myc oncogene, FGFR3 (fibroblast growth factor receptor 3), MMSET (multiple myeloma SET domain), MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4), and the c-maf oncogene, respectively. However, the cellular biological roles of these genes have not yet been elucidated in myeloma cells. Because two of the seven human myeloma cell lines which were established at Kawasaki Medical School, Okayama, Japan, KMS-11 and KMS-18, have been proven to possess t(4;14)(q16.3;q32.3), we studied the expression levels of the FGFR3 gene in these seven cell lines and 13 primary myeloma specimens. The expression levels of 12 known FGF family genes (FGF-1 to 12) and 4 FGFR genes (FGFR1 to 4) were also examined in seven cell lines. In addition, the growth status of the KMS-11 and KMS-18 lines with FGF-1 or anti-FGF-4 neutralizing monoclonal antibody (MoAb) supplementation was investigated because FGF-1 and 4 are known as the principal ligands for FGFR3. FGFR3 overexpression was observed in both of the cell lines possessing t(4;14)(q16.3;q32.3) and in 3 of 13 case specimens. Anti-FGF-4 neutralizing MoAb caused significant growth inhibition in these two cell lines possessing t(4;14)(q16.3;q32.3). These findings indicate that t(4;14) (q16. 3;q32.3) may provide myeloma cells with a growth advantage via an autocrine mechanism between FGFR3 and FGF-4.

Aged↗
PubMed2006

Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades.

WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are transduced through Frizzled receptor and LRP5/6 coreceptor to downregulate GSK3beta (GSK3B) activity not depending on Ser 9 phosphorylation. FGF signals are transduced through FGF receptor to the FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and degradation, GSK3beta downregulation results in the stabilization and the nuclear accumulation of beta-catenin and SNAIL. Nuclear beta-catenin is complexed with TCF/LEF, Legless (BCL9 or BCL9L) and PYGO (PYGO1 or PYGO2) to activate transcription of CCND1, MYC, FGF18 and FGF20 genes for the cell-fate determination. Nuclear SNAIL represses transcription of CDH1 gene, encoding E-cadherin, to induce the epithelial-mesenchymal transition (EMT). Mammary carcinogenesis in MMTV-Wnt1 transgenic mice is accelerated by MMTV infection due to MMTV integration around Fgf3-Fgf4 or Fgf8 loci, and mammary carcinogenesis in MMTV-Fgf3 transgenic mice due to MMTV integration around Wnt1-Wnt10b locus. Coactivation of WNT and FGF signaling pathways in tumors leads to more malignant phenotypes. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of WNT and FGF signaling molecules could be utilized as screening method of cancer predisposition. cDNA-PCR, microarray or ELISA reflecting aberrant activation of WNT and FGF signaling pathways could be developed as novel cancer-related biomarkers for diagnosis, prognosis, and therapy. Cocktail therapy using WNT and FGF inhibitors, such as small-molecule compounds and human neutralizing antibodies, should be developed to increase the efficacy of chemotherapy through the inhibition of recurrence by destructing cancer stem cells.

Animals↗
PubMed1999

O-linked carbohydrates are required for FGF-2-mediated proliferation of mouse embryonic cells.

During development, fibroblast growth factors (FGFs) serve highly specific functions that are mediated through high-affinity transmembrane receptors and modulated by membrane-bound proteoglycans. Proteoglycans, in an embryonic environment called embryoglycans, contain numerous carbohydrate ectodomains, the structure of which undergoes rearrangement. Since they can be lost from the cell surface, they are sometimes found in extracellular space where they may also serve some regulatory function. Here we address the potential roles of three naturally occurring isoforms of Lewis X (LeX) in FGF-2-mediated proliferation of embryonic stem (ES) cells. We have found that the addition of sulfated LeX to ES cells at a concentration of 17 nM promotes FGF-2 mitogenic activity while a 10-fold higher concentration leads to a reduction of FGF-2-mediated proliferation. Notably, this dose-dependent modulation operated only for sulfated LeX. Other fucosylated motifs, basic LeX trisaccharide and sialylated LeX, also affected ES cell proliferation but the mechanism cannot be clearly correlated with the presence or absence of FGF-2. The suppression of biosynthesis of O-linked carbohydrates including LeX reduced basal proliferation of ES cells and interfered with the mitogenic effect of FGF-2. However, in inhibitor-treated cells, the stimulatory activity of FGF-2 can be reestablished to its original level by exogenous LeX oligosaccharides. Our results show that (A) O-linked LeX oligosaccharides can regulate mitogenic activity of FGF-2 in embryonic cells, (B) and this ability varies with subtle modifications in their structure. Importantly, our data represent the first insight into the mechanism of how growth factor activities might be modulated by shedded embryoglycan ectodomains.

Animals↗
PubMed2001

FGF signaling is essential for the early events in the development of the chick nervous system and mesoderm.

Fibroblast growth factor (FGF) belongs to a family of polypeptides with diverse biological functions. In the present study we have assessed the role of FGF signaling in the development of nervous system and mesodermal tissues in chick embryo. Treatment of in vitro cultured embryos with exogenous, human recombinant FGF led to abnormalities in neural induction and development, notochord formation and somitogenesis as studied by gross morphology and histology. Overall growth and development was also adversely affected as seen from the measurement of body axis length. Further, treatment of embryos with FGF resulted in differential modulation of expression of two genes important in normal development as studied by whole mount in situ hybridization using DIG-labeled riboprobes. The expression of Brachyury, which is necessary for mesoderm formation, was down-regulated in FGF-treated embryos. The expression of noggin, the product which participates in the patterning of the chick neural tube was, on the other hand, up-regulated within 2 h. We also studied development of neural and mesodermal tissues in conditions where FGF signaling was defective. This was achieved by culturing the embryos in the presence of suramin. In the presence of low doses of suramin (100-150 nmole/culture), abnormalities were detected mainly in the mesodermal structures while at higher doses (200-400 nmole/culture), the nervous system too was found to be abnormal in a large proportion of embryos. Treatment of chick embryos with suramin (200 nmole/culture) also modulated the expression of Brachyuryand noggin within a 2 h period. The results showthat FGF signaling plays an important role in the molecular events leading to the development of nervous system and mesodermal tissues in the chick embryo.

Animals↗
PubMed2002

WNT and FGF gene clusters (review).

Mouse mammary tumor virus (MMTV) is a retrovirus, activating Wnt genes (Wnt1/int-1, Wnt3/int-4, Wnt10b), Fgf genes (Fgf3/int-2, Fgf4, Fgf8) and other genes (Notch4/int-3, Eif3s6/int-6) due to proviral integration. Among 19 WNT genes, WNT3 and WNT14B genes are clustered in human chromosome 17q21, WNT3A and WNT14 in human chromosome 1q42, WNT10A and WNT6 in human chromosome 2q35, and WNT10B and WNT1 in human chromosome 12q13. Among 22 FGF genes, FGF19, FGF4 and FGF3 genes are clustered in human chromosome 11q13, while FGF23 and FGF6 in human chromosome 12p13. WNT and FGF gene clusters are conserved between the human genome and the mouse genome. Activation of mouse Wnt or Fgf genes due to proviral integration of MMTV occurs in 5 out of 13 clustered genes, and in 1 out of 28 solitary genes (p=0.0033), which clearly indicates that mouse Wnt or Fgf gene clusters are recombination hot spots associated with carcinogenesis. Recombination results in retroviral integration as well as in chromosomal translocation, gene amplification and deletion during carcinogenesis. The CCND1-FGF19-FGF4-FGF3 gene cluster in human chromosome 11q13 is amplified in breast cancer, squamous cell carcinoma of head and neck, and bladder tumors, and is also translocated in parathyroid tumors and B-cell lymphoma. WNT gene clusters on human chromosome 1q42, 2q35, 12q13, and 17q21 as well as FGF gene cluster on human chromosome 12p13 might be amplified or translocated in human cancer just like FGF gene cluster on human chromosome 11q13.

Animals↗
PubMed2005

Immunolocalization of fibroblast growth factor-2 (FGF-2) during embryonic development of the rat submandibular gland.

Morphogenesis and cytodifferentiation of the salivary glands are dependent on epithelio-mesenchymal interactions, which are mediated either by direct intercellular contacts or by the expression of signaling molecules. One of these signaling molecules, fibroblast growth factor (FGF), is known to play a crucial role in embryonic cell proliferation, cell differentiation and cell migration. FGF-2 has been identified as a factor facilitating neoplastic progression in salivary glands in humans. The aim of this study was to elucidate the spatial and temporal expression of fibroblast growth factor-2 (FGF-2) in the developing rat submandibular gland. Submandibular glands were removed from foetal rats on days E14.5, 15.5, 16.5, 18.5 and 19.5. Immunolocalization utilizing an antibody to FGF-2 was performed on sections of the submandibular gland at all the derived stages. Diffuse and faint immunolocalization of FGF-2 was seen in the epithelium and mesenchyme of the submandibular gland on days E14.5, E15.5 and E16.5. Intense immunoreactivity for FGF-2 was observed in epithelial components of the gland i.e. in the differentiating acini and ducts, on day E18.5, while on day E19.5, the signal was again less intense. These observations suggest that FGF-2 may play a specific role in cytodifferentiation of the submandibular gland at a particular stage of development.

Animals↗
PubMed2005

[Expression and clinical significance of PTTG and b-FGF in acute leukemia].

To investigate the expression of pituitary tumor-transforming gene (PTTG) and basic fibroblast growth factor (b-FGF) in acute leukemia, as well as the relationship of their expression with prognosis in acute leukemia, expressions of PTTG and b-FGF in acute leukemia (AL) specimens were detected by immunocytochemical technique. The results showed that the expressions of PTTG and b-FGF in AL group were higher than that in the control group significantly (P < 0.01). In AL group, after chemotherapy, the expression of PTTG and b-FGF in de novo patients group was higher than in the complete remission patient group significantly (P < 0.01). The expressions of PTTG and b-FGF showed positive correlation (r = 0.61, P < 0.01). It is concluded that Up-regulation of PTTG and b-FGF expression may be involved in the progression of acute leukemia and correlated closely with therapeutic effect. Associated detection of PTTG and b-FGF may help to judge the malignancy degree and prognosis of acute leukemia.

Acute Disease↗
PubMed2005

Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes.

Chondrocyte preparation with the safety and efficiency is the first step in cartilage regenerative medicine. To prepare a chondrocyte proliferation medium that does not contain fetal bovine serum (FBS) and that provides more than a 1000-fold increase in cell numbers within approximately 1 month, we attempted to use the medium containing 5% human serum (HS), but it exerted no more than twofold increase in 2 weeks. To compensate for the limited proliferation ability in HS, we investigated the combinational effects of 12 factors [i.e., fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-I, insulin, bone morphogenetic protein-2, parathyroid hormone, growth hormone, dexamethasone, 1alpha25-dihydroxy vitamin D3, L-3,3',5'-triodothyronine, interleukine-1 receptor antagonist, 17beta-estradiol, and testosterone] on the proliferation of human auricular chondrocytes by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number synergistically gained a 10-12-fold increase with 5 microg/ml insulin or 100 ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a concentration of 100 ng/ml for FGF-2, and especially for the combination of 100 ng/ml FGF-2 and 5 microg/ml insulin (approximately 16-fold within 2 weeks). In the long-term culture with repeated passaging, this combination provided more than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration.

Adolescent↗
PubMed2005

Opposite effects of beta amyloid on endothelial cell survival: role of fibroblast growth factor-2 (FGF-2).

Amyloid beta-peptides (Abeta) aggregate during Alzheimer's disease contributing to the development of the pathology. At micromolar concentration Abeta is toxic and accumulates in neurons and in the vasculature. However, Abeta is found at nanomolar concentrations in the plasma of healthy individuals and is also produced by endothelial cells. Here, we investigate the dual role exerted by Abeta(1-40) on endothelial cell functions. Coronary vascular endothelial cells were utilized to study whether Abeta affects endothelial cell growth and its action was compared with the effect of fibroblast growth factor-2 (FGF-2). In a range from 5 to 100 nM, Abeta(1-40) concentration-dependently increased cell growth, whereas higher concentrations of Abeta(1-40) reduced cell number compared to control. At nanomolar concentration of the peptide Abeta(1-40) also stimulated FGF-2mRNA expression and protein production, which was negatively affected by micromolar concentration of the peptide. The dual role observed on endothelial cell growth, was mediated by FGF-2 biodisponibility. In fact, neutralizing anti-FGF-2 antibody inhibited Abeta(1-40)-induced ERK1/2 phosphorylation at 50 nM. 5 muM inhibited ERK1/2 activation over control and this was reflected by diminished cell growth which was recovered by exogenous FGF-2 administration. These results suggest that low Abeta concentrations stimulate endothelial cells to acquire an angiogenic phenotype through interaction with endogenous FGF-2 and induction of its synthesis. In contrast, accumulation of Abeta results toxic for endothelial cells and at these concentrations Abeta peptide looses its ability to prime FGF-2 cycle. This may be a fundamental pathological event which might contribute to the worsening of the pathology.

Amyloid beta-Peptides↗
PubMed1991

[The change in immunohistochemical localization of basic fibroblast growth factor (b-FGF) around the lens capsule after extracapsular extraction].

It has been reported that basic fibroblast growth factor (b-FGF) accelerates proliferation of mesenchymal cells and epithelial cells of cornea and crystalline lens in vitro. The immunohistochemical localization of b-FGF on guinea pig lens capsule after extracapsular extraction (ECE) of the lens was studied in order to investigate the role of b-FGF on posterior capsular opacification after ECE and neovascularization. On the 12th postoperative day, immunohistochemical staining of b-FGF was recognized along the posterior capsule on the cortical side, but not along the anterior capsule. On non-operated eyes, scanty immunoreactive materials were seen in cells at the germinative center of the equatorial region. More than two months after ECE, almost no immunoreactive staining could be recognized. In this study, immunoreactive staining of b-FGF was recognized along the posterior capsule on cortical side after operation. It has also been reported that b-FGF stimulates proliferation of the lens epithelial cells in vitro. Therefore, it is suggested that b-FGF plays an important role on posterior capsular opacification after cataract formation.

Animals↗