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Biomedical subjects

D Gospodarowicz

Publications and source records attributed to D Gospodarowicz.

At least 37 records · Page 2Linked to original sources
PubMed1990

Fibroblast growth factor. Chemical structure and biologic function.

Basic and acidic fibroblast growth factor (FGF) are two closely related growth factors that interact with the same receptor. Structurally related to FGF are five different oncogenes that have been involved in mammary, stomach, and bladder cancers but whose precise functions in physiologic processes are presently unknown. Both basic and acidic FGF exert similar biologic effects on a wide range of mesoderm- and neuroectoderm-derived cells, acting both as morphogens and mitogens. In addition, basic FGF has been shown to act as a ventrovegetalizing factor, inducing, at the midblastulae stage, mesoderm formation from animal pole cells destined to form ectodermal structures. This primordial role explains the wide variety of tissues, ranging from the central and peripheral nervous system to the vascular system, that are affected by FGF during the late embryonic, neonatal, and adult phases of development.

Animals↗
PubMed1989

Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family.

Using applications of the polymerase chain reaction (PCR) technique, cDNA clones have been isolated encoding bovine vascular endothelial growth factor (VEGF), a mitogen with specificity for vascular endothelial cells. Analysis of the clones indicates that VEGF can exist in two forms, probably due to alternative RNA splicing. The amino acid sequences predicted from the clones also show that VEGF shares homologies of about 21% and 24% respectively with the A and B chains of human platelet-derived growth factor (PDGF), and has complete conservation of the eight cysteine residues found in both mature PDGF chains. The homology is not reflected in function, however, since the cell types responsive to VEGF are distinct from those responsive to homo- and heterodimers of the PDGF chains.

Amino Acid Sequence↗
PubMed1989

Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells.

An endothelial cell growth factor with unique specificity for vascular endothelial cells has been purified from the conditioned medium of the AtT-20 pituitary cell line. This growth factor, which has been characterized as a homodimer composed of two subunits with mol. wts of 23 kd is a potent mitogen for vascular endothelial cells in vitro with activity detectable at 50 pg/ml and saturation at 1 ng/ml. It was also angiogenic in vivo. In contrast with other endothelial mitogens of the fibroblast growth factor family, it has a unique target cell specificity. It did not stimulate the growth of other cell types of the vascular system such as vascular smooth muscle cells or that of mesoderm and neuroectoderm derived cells. Microsequencing revealed an amino-terminal sequence with no homology to any known protein. The release of this novel endothelial cell growth factor by pituitary derived cells and its unique target cell specificity suggest that it could play an important role in the angiogenic process.

Amino Acid Sequence↗
PubMed1989

Pituitary follicular cells secrete both vascular endothelial growth factor and follistatin.

Follistatin, a hormone which acts to suppress the release of follicle-stimulating hormone (FSH) by pituitary-derived gonadotrophs, has previously been identified only in the liquor folliculi of ovarian follicles. By microsequencing of fractions derived from conditioned medium, we show here that bovine pituitary-derived folliculo stellate cells are also capable of producing and secreting this hormone. These results suggest that folliculo stellate cells may serve as a source of follistatin within the pituitary itself and that the regulation of FSH release from the pituitary could therefore involve a paracrine mechanism.

Adrenal Cortex↗
PubMed1989

Structural analysis of the gene for human acidic fibroblast growth factor.

Genomic clones derived from the gene for human acidic fibroblast growth factor (aFGF) have been isolated. Nucleotide sequence analysis of these clones revealed that the coding region of the human aFGF gene is interrupted by two introns, located at precisely homologous locations to introns in four other members of the FGF gene family, strongly indicating a common evolutionary origin for these genes. Northern blot analyses of the multiple aFGF transcripts found in serum-stimulated human foreskin fibroblasts indicated that the aFGF gene also contains a third intron, lying in the 5' untranslated region.

Amino Acid Sequence↗
PubMed1989

Transforming growth factor beta-1 positively modulates the bioactivity of fibroblast growth factor on corneal endothelial cells.

Transforming growth factor beta-1 (TGF beta-1), known as an inhibitor of vascular endothelial cell proliferation in vitro, stimulates bovine corneal endothelial cells (BCE) proliferation. It also positively modulates the response of BCE cells to fibroblast growth factor (FGF) and epidermal growth factor (EGF). This effect is concentration dependent within a physiological range of TGF beta-1, but it is blocked if cells are cultured on extracellular-matrix-coated dishes instead of plastic. TGF beta-1 does not modify the number or the affinity of bFGF receptors on BCE cell surface but increases the bFGF content of these cells. This suggests that TGF beta-1 might act through regulation of bFGF synthesis in BCE cells.

Animals↗
PubMed1989

Fibroblast growth factor and the control of pituitary and gonad development and function.

Evidence from in vitro studies support the concept that growth factors could be involved in the development, maturation and function of endocrine organs. Included among the growth factors which are known to influence endocrine cell proliferation and differentiation is the fibroblast growth factor (FGF), which controls the proliferation, differentiation, and other functions of mesodermal- and neuroectodermal-derived cells. Its modulator, transforming growth factor beta (TGF beta), which determines the positive or negative direction of the effects of FGF, may play a role as well. In this review, we present a speculative view of how FGF in the pituitary gland, and both FGF and TGF beta in the gonads could influence the development and function of these organs through regulating mechanisms involving paracrine and autocrine control of cell proliferation and differentiation.

Aging↗
PubMed1989

Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells.

A growth factor with specificity for vascular endothelial cells has been identified in conditioned medium of pituitary-derived folliculo stellate cells. This factor, named folliculo stellate-derived growth factor (FSdGF), was purified to homogeneity by a combination of heparin-Sepharose affinity chromatography, Bio-Gel P-60 exclusion chromatography, Mono S ion-exchange chromatography, and hydrophobic chromatography on a C4 reverse-phase HPLC column. FSdGF was characterized as a homodimer composed of two subunits with a molecular mass of 23 kDa. FSdGF was a potent mitogen for vascular endothelial cells with activity detectable at 25 pg/ml and saturation at 500 pg/ml. It did not stimulate the proliferation of other cell types such as bovine vascular smooth muscle cells, corneal endothelial cells, adrenal cortex cells, granulosa cells, BALB/MK cells, or BHK-21 cells. Microsequencing revealed an N-terminal sequence having no significant homology to any known protein. The release of FSdGF by pituitary cells and its target cell specificity raise the possibility that FSdGF may play a role in angiogenesis.

Animals↗
PubMed1989

Expression and control of vascular endothelial cells: proliferation and differentiation by fibroblast growth factors.

Evidence from in vitro studies supports the concept that growth factors could be involved in the development and function of the vascular tree. Among the growth factors known to influence vascular endothelial cells' proliferation and differentiation, in vitro, are the fibroblast growth factors. These consist of two closely, structurally, related polypeptides that differ by their isoelectric point and have been called basic and acidic fibroblast growth factor. These growth factors, in particular basic fibroblast growth factor, which is expressed and synthesized by vascular endothelial cells, could influence the development, remodeling, and function of the vascular tree through regulating mechanisms involving paracrine and autocrine control of cell proliferation and differentiation.

Animals↗
PubMed1989

Cultured bovine bone cells synthesize basic fibroblast growth factor and store it in their extracellular matrix.

Bone contains various growth factors, including fibroblast growth factor (FGF). The cellular origins of the growth factors found in bone are not known. We examined whether cultured fetal bovine bone cells synthesize FGF. These cells express characteristic markers of the osteoblast phenotype, including expression of bone Gla protein (osteocalcin) and mineralization. Heparin-Sepharose fractionation of cell extracts revealed that bone cells contained a basic FGF (bFGF)-like molecule, that displayed high affinity for heparin. The growth factor was mitogenic for adrenal cortex-derived endothelial cells and osteoblast-like bone cells. The major peak of biological activity corresponded to a peak of immunoreactive bFGF. When analyzed by Western blot, the active fractions contained a bFGF-like immunoreactive species with a mol wt of 15,000, a mass identical to that of (des-1-15)bFGF. Based on RIA, the bone cell extract contained an estimated 95 ng bFGF/mg cell protein. An acidic FGF-like molecule with lower affinity for heparin was also present in the purified bone cell extracts, although at an approximately 10-fold lower concentration than bFGF. These results demonstrate that bone cells synthesize a mitogen indistinguishable from bFGF. In addition, Northern analysis revealed that the bone cells expressed 3.5- and 7.0-kilobase bFGF gene transcripts. We next examined whether the bone cell-derived bFGF is stored in a bioactive form in the extracellular matrix. Bone cells synthesized an extracellular matrix which was mitogenic for adrenal cortex-derived endothelial cells. However, if the bone cell extracellular matrix was preincubated with neutralizing anti-bFGF antibodies, its mitogenic properties were abolished. This suggests that bone cell-derived bFGF may function as an autocrine or paracrine mitogen via its deposition into the extracellular matrix of bone.

Adrenal Cortex↗
PubMed1989

Ovarian germinal epithelial cells respond to basic fibroblast growth factor and express its gene: implications for early folliculogenesis.

Cultured bovine ovarian germinal epithelial (OGE) cells respond to fibroblast growth factor (FGF) with an increased rate of proliferation. The basic form of FGF (bFGF) had an ED50 of 110 pg/ml, while the acidic form had an ED50 of 3.5 ng/ml. The mitogenic effect of FGF was blocked by transforming growth factor-beta. OGE cells express the gene encoding bFGF. The bFGF gene is transcribed into 7.0- and 3.7-kilobase mRNA transcripts, which are translated into 18,600 mol wt bFGF-like growth factor. OGE-derived bFGF is bioactive and stimulates the proliferation of capillary endothelial cells or OGE cells. This mitogenic effect is prevented by specific neutralizing anti-bFGF antibodies. Our results indicate that bFGF derived from OGE cells can act as both autocrine and paracrine growth factor for that cell type, and they further suggest that the factor may be involved in the development of early follicles.

Actins↗
PubMed1988

Regulation of ion transport in hypophysial pars intermedia follicular cell monolayers.

We have previously reported that cultured monolayers of folliculo-stellate cells (FC) of adenohypophysial pars tuberalis (PT) and pars distalis (PD) origin express morphological and electrical properties typical of ion and fluid transporting epithelia. The objective of the present study was to examine whether cells expressing similar transport properties exist also in the pars intermedia (PI), an area of the adenohypophysis very poorly vascularized, where a cell type expressing such functions would be expected to play an especially significant role in the local regulation of the interstitial fluid content and circulation. Enzymatically and mechanically dispersed bovine pars intermedia fragments yield monolayers of polygonal, contact inhibited cells which rapidly develop domes. Such cells exhibit morphological features and growth properties very similar or identical to those expressed by cells previously identified af FC cells in PD and PT cultures. Similarly to their counterparts in the PD and PT, the PI FC display a potential difference and a resistance when mounted in Ussing chambers. Isoproterenol, prostaglandin E2, bradykinin and lysine vasopressin are able to stimulate active ion transport across FC monolayers. These data indicate that the PI contains ion transporting FC and suggest important local regulatory functions for these cells.

Animals↗
PubMed1988

Bovine brain astrocytes express basic fibroblast growth factor, a neurotropic and angiogenic mitogen.

Astrocytes derived from adult bovine corpus callosum contain large amounts of mitogenic activity for capillary endothelial cells and astrocytes. On the basis of radioimmunoassay, bioassay and immunoneutralization studies, 99.5% of this activity consists of basic fibroblast growth factor (bFGF). Immunoblot and gene expression analysis are also consistent with the synthesis of bFGF. The remainder of bioactivity [0.5%] is accounted for by acidic fibroblast growth factor (aFGF). These data suggest that astrocytes are a source of brain-derived bFGF and to a much lesser extent also of aFGF. Considering that bFGF has been proposed to play a role in the development and differentiation of the nervous system through its angiogenic and neurotropic properties, its presence in astrocytes provides a rationale for the complex regulatory and neurotropic functions attributed to these cells. Also, the ability of bFGF to stimulate the growth of astrocytes themselves suggest a role for the mitogen in normal and aberrant proliferation of astrocytes.

Animals↗
PubMed1988

Identification of the fibroblast growth factor receptor in human vascular endothelial cells.

The fibroblast growth factor (FGF) receptor of human umbilical vein-derived endothelial (HUE) cells has been identified by affinity labeling. It has an apparent molecular weight of 130,000. It binds both basic and acidic FGF, but not with epidermal growth factor, insulin, or transferrin. The lectin concanavalin-A does not inhibit the binding of 125I-bFGF to HUE cell-surface receptors, whereas it inhibits bFGF binding to BHK-21 cell-surface FGF receptor. This suggests that both types of receptors may differ in their degree of glycosylation. In contrast to other cell types, heparin only slightly inhibits the binding of basic FGF to its receptor. Protamine sulfate, which is anti-angiogenic in vivo, and suramin, a drug used in the therapy of trypanosomiasis and onchocerciasis, also inhibit the binding of basic FGF to the receptor.

Affinity Labels↗
PubMed1988

Basic fibroblast growth factor as a regulator of ovarian granulosa cell differentiation: a novel non-mitogenic role.

The role of basic fibroblast growth factor (bFGF) in ovarian granulosa cell differentiation was investigated in vitro. To this end, use was made of a primary culture of rat granulosa cells the differentiation of which was monitored by the acquisition of aromatase activity. Concurrent treatment with highly purified bFGF (10 ng/ml) produced a significant (P less than 0.05), albeit reversible inhibition (88 +/- 6%) of FSH (but not basal)-supported aromatization. Although independent of the FSH dose employed and of cell density, bFGF-attenuated aromatase activity proved dose-dependent, with a projected minimal effective dose of 0.11 +/- 0.03 ng/ml (7.5 +/- 2 pM), and an apparent median inhibitory dose of 0.63 +/- 0.09 ng/ml (43 +/- 6 pM). Unaccounted for by alterations in granulosa cell number, plating efficiency, or viability, the ability of bFGF to attenuate FSH hormonal action proved partly attributable to site(s) of action distal, rather than proximal to cAMP generation. Taken together, these observations indicate that the cytodifferentiative and replicative actions of bFGF in the granulosa cell can be dissociated, and lend additional support to the prospect that bFGF, possibly of intraovarian origin, may play a role in granulosa cell differentiation in the course of their ontogeny.

Animals↗
PubMed1988

Basic fibroblast growth factor: expression in cultured cells derived from corneal endothelium and lens epithelium.

We have examined the possible expression of fibroblast growth factor in cultured cells derived from bovine lens epithelium and corneal endothelium. Lens epithelial, but not corneal endothelial, cells were found to express the acidic fibroblast growth factor (aFGF) gene, whereas both cell types express the gene encoding basic fibroblast growth factor (bFGF), a related mitogen. Expression of bFGF was further examined. Both corneal endothelial and lens epithelial contain 3.7 and 7.0 k bFGF gene transcript, which are translated into material closely related, if not identical with bFGF. Essentially all of the bFGF-like material is bioactive, i.e. it can stimulate the proliferation of capillary endothelial or corneal endothelial cells and the stimulation is blocked by anti-bFGF antibodies. Our results indicate that bFGF derived from corneal endothelial and lens epithelial cells may act as a paracrine and autocrine growth factor in both cell types. Thus, bFGF present in both cell types may play an important role in the proliferation of injured or transformed ocular tissues.

Animals↗