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PubMed2002

Elevated expression of hepatocyte and keratinocyte growth factor in cultured buccal-mucosa-derived fibroblasts compared with normal-skin-derived fibroblasts.

Oral mucosa heals faster with less scar formation than skin and a hypertrophic scar is very rare in the oral cavity, but its mechanism has not been elucidated enough. To elucidate whether or not there are differences in growth factor expression between fibroblasts derived from buccal mucosal and normal skin, we investigated the expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and stem cell factor (SCF) by cultured fibroblasts. The semiquantitative RT-PCR revealed that the expression of HGF and KGF transcripts by buccal mucosal fibroblasts was significantly elevated compared with that by dermal fibroblasts. In parallel, ELISA revealed the significant increase of HGF production by buccal mucosal fibroblasts. The level of production of SCF protein did not differ significantly. Our study suggests that increased expression of HGF and KGF by buccal mucosal fibroblasts may partly be responsible for the faster wound healing with less scar formation in the oral cavity compared with normal skin.

Adolescent↗
PubMed1997

Significance of basic fibroblast growth factor and fibroblast growth factor receptor protein expression in the formation of fibrotic focus in invasive ductal carcinoma of the breast.

A fibrotic focus (FF) is a scar-like area within invasive ductal carcinoma (IDC) of the breast, and has been shown to be a marker of high aggressiveness of IDC. In order to investigate the mechanism of FF formation in IDC, expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) was studied. One hundred and forty-nine IDCs were divided into solid tumors and scirrhous tumors. Immunohistochemistry was used to determine the expression of bFGF and FGFR proteins in both tumor cells and fibroblasts forming FF. Scirrhous tumors with FF showed a significantly higher frequency of bFGF protein expression than those without (P = 0.017), whereas, in solid tumors, the presence of FF was not significantly associated with the frequency of bFGF protein expression (P = 0.143). In addition, scirrhous tumors showed a significantly higher frequency of FGFR protein expression than solid tumors (P = 0.001). Among IDCs having FF and expressing bFGF protein, a significantly larger number of fibroblasts expressing FGFR protein within FF was observed in scirrhous tumors than in solid tumors (P = 0.016). The results of this study suggest that in scirrhous tumors the interaction between tumor cells and stromal fibroblasts plays an important role in the formation of FF, and that there is a paracrine mechanism between bFGF protein from tumor cells and FGFR protein in fibroblasts.

Adenocarcinoma, Scirrhous↗
PubMed1992

Tumor promoters induce basic fibroblast growth factor gene expression in human dermal fibroblasts.

Tumor-promoting phorbol esters have been shown previously to either induce or repress the expression of numerous cellular genes, and this property is likely to be important for the in vitro and in vivo biological effects of these compounds. In this report, we demonstrate that phorbol 12-myristate 13-acetate induces the accumulation of basic fibroblast growth factor mRNA and protein in human dermal fibroblasts. In contrast, acidic fibroblast growth factor expression was unaffected by this compound. The enhancement of basic fibroblast growth factor gene expression by phorbol 12-myristate 13-acetate was blocked by the isoquinolinesulfonamide derivative H7, a potent inhibitor of protein kinase C. Two additional tumor promoters that bind to and activate protein kinase C, phorbol 12,13-didecanoate and mezerein, also increased basic fibroblast growth factor mRNA levels. Basic fibroblast growth factor is a mitogen for many cell types and can stimulate angiogenesis; thus, some tumor promoter-induced cellular responses may be mediated by this polypeptide.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

The effect of silicone gel on basic fibroblast growth factor levels in fibroblast cell culture.

BACKGROUND: Topical silicone gel has shown promise in the treatment of hypertrophic and keloid scars. However, its mechanism of action remains undetermined. OBJECTIVE: To investigate whether the presence of silicone alters the secretion of basic fibroblast growth factor (bFGF), a key cytokine involved in the scar formation process. DESIGN: Serum-free fibroblast cell cultures were established from normal, keloid, and fetal skin, which heals without scarring, and exposed to silicone gel. Serial cell counts were performed, and supernatants were collected for bFGF quantification by enzyme-linked immunosorbent assay at 4, 24, 72, and 120 hours. RESULTS: Growth curves were similar and no statistically significant differences in population doubling times were observed between treated and untreated specimens. Statistically significant differences in bFGF levels between treated and untreated normal fibroblasts were observed at 24, 72, and 120 hours after cell culture initiation. Differences in bFGF levels between treated and untreated fetal fibroblasts that approached statistical significance were observed at 72 and 120 hours. CONCLUSIONS: These results suggest that silicone gel is responsible for increased bFGF levels in normal and fetal dermal fibroblasts. We postulate that silicone gel treats and prevents hypertrophic scar tissue, which contains histologically normal fibroblasts, by modulating expression of growth factors such as bFGF. Our data support the hypothesis that substances that favorably influence wound healing do so by correcting a deficiency or overabundance of the growth factors that orchestrate the tissue repair process.

Adolescent↗
PubMed1989

Growth of normal human keratinocytes and fibroblasts in serum-free medium is stimulated by acidic and basic fibroblast growth factor.

Keratinocytes and fibroblasts isolated from human neonatal foreskin can be plated and grown through multiple rounds of division in vitro under defined serum-free conditions. We utilized these growth conditions to examine the mitogenic potential of acidic and basic fibroblast growth factor (aFGF and bFGF) on these cells. Our results demonstrate that both aFGF and bFGF can stimulate the proliferation of keratinocytes and fibroblasts. aFGF is a more potent mitogen than bFGF for keratinocytes. In contrast, bFGF appears to be more potent than aFGF in stimulating the growth of fibroblast cultures. Heparin sulfate (10 micrograms/ml) dramatically inhibited the ability of bFGF to stimulate the proliferation of keratinocytes. In comparison, heparin slightly inhibited the stimulatory effect of aFGF and had no effect on epidermal growth factor (EGF) stimulation in keratinocyte cultures. In fibroblast cultures the addition of heparin enhanced the mitogenic effect of aFGF, had a minimal stimulatory effect on the mitogenic activity of bFGF, and had no effect on EGF-stimulated growth. Our results demonstrate that the proliferation in vitro of two normal cell types found in the skin can be influenced by aFGF and bFGF and demonstrate cell-type specific differences in the responsiveness of fibroblasts and keratinocytes to these growth factors and heparin.

Cell Division↗
PubMed1994

Epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, acidic fibroblast growth factor, basic fibroblast growth factor, and interleukin-1 proteins in the cornea.

The purpose of this study was to determine whether epidermal growth factor (EGF), EGF receptor, transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta), acidic fibroblast growth factor (acidic-FGF), basic fibroblast growth factor (basic-FGF), and interleukin-1-alpha (IL-1-alpha) proteins were present in cultures of human corneal cells and/or in sections of human corneal tissue. Immunohistochemistry was performed on human corneal sections. Immunofluorescent cell staining was used to evaluate corneal epithelial, stromal fibroblast, and endothelial cells in primary culture. Basic-FGF production was evaluated in culture cells using immunoprecipitation. EGF, TGF-alpha, TGF-beta-1, and IL-1-alpha were detected by immunohistochemistry in cells in all three layers of the cornea. EGF receptor and acidic FGF were detected by immunohistochemistry in epithelial and endothelial cells, but not in stromal fibroblast cells. Differences in distribution of the growth factors were noted within individual layers of the cornea. EGF and basic-FGF proteins were detected in all three predominant cell types of the cornea using immunocytology. IL-1-alpha protein was detected by immunocytology in corneal epithelial and endothelial cells, but not stromal fibroblasts. Immunoprecipitation confirmed the production of basic-FGF in all three cell types. IL-1-alpha protein detection in the corneal stroma by immunohistology, but not by immunocytology in first passage stromal fibroblasts, suggests that IL-1-alpha may localize to the corneal stroma after production by corneal epithelial and/or endothelial cells.

Adult↗
PubMed2000

Ultrastructural immunolocalization of basic fibroblast growth factor in fibroblasts and extracellular matrix.

Basic fibroblast growth factor (bFGF) is thought to play an important role in normal tissue repair and wound healing. It is a potent mitogenic and chemotactic factor for fibroblasts, regulating proliferation and extracellular matrix (ECM) production by these cells. In this study, we present morphologic evidence of the ultrastructural location of bFGF in fibroblasts and ECM using several antibodies, tissues, and species. Distinct labeling is seen in the nuclei of fibroblasts and some labeling in the cytosol. Immunolabeling of the cytosol excludes organelles involved in the usual secretory pathway, such as rough endoplasmic reticulum, Golgi apparatus, and secretory vacuoles. The same labeling is observed with either polyclonal or monoclonal antibodies. We suggest that bFGF functions as a nuclear protein in fibroblasts and is not secreted by a normal secretory pathway. Fibroblasts may export bFGF via unique cellular pathways that are clearly distinct from classic signal peptide mediated secretion. This may provide a source for ECM-resident bFGF. The same antibodies show different labeling intensity in the ECM. This protein, through integration into the ECM, may act as a local regulator and promote regeneration of these tissues after wounding. Direct evidence is the dramatic reduction of bFGF labeling in axotomized rat ECM collagen fibers versus control animals.

Adrenal Glands↗
PubMed1998

Expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and hepatocellular carcinoma.

This study was performed to examine the immunohistochemical expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and a total of 31 cases of hepatocellular carcinoma (HCC). Reactivity for both types of angiogenic factor did not exist in any cellular component of normal liver. For HCC, variable amounts of fibroblast growth factor-1 were detected in 6 of 31 cases (19.4%). There was no apparent relationship between the expression pattern and clinicopathologic factors (P > 0.1, respectively), except a positive correlation with histologic grading (P = 0.04). No tumor showed reactivity for fibroblast growth factor-2 in their cancer cells. However, both types of peptide could be demonstrated in the pericellular stroma of HCC. With a mean follow-up at 60 months, fibroblast growth factor-1 expression did not correlate with patients' outcome (P > 0.1). Our study suggested that fibroblast growth factor-1 appears to play a certain role in hepatocarcinogenesis.

Adolescent↗
PubMed1994

Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers.

The human fibroblast activation protein alpha (FAP alpha) is a M(r) 95,000 cell surface antigen selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. Normal adult tissues are generally FAP alpha-, but some fetal mesenchymal tissues transiently express the molecule. Because of its restricted normal tissue distribution and abundant expression in the stroma of over 90% of breast, colorectal, and lung carcinomas, FAP alpha is under clinical evaluation as a target for immunodetection and immunotherapy of epithelial cancers. In the present study, we have isolated a full-length cDNA for FAP alpha through expression cloning in COS-1 cells. The FAP alpha cDNA codes for a type II integral membrane protein with a large extracellular domain, transmembrane segment, and short cytoplasmic tail. FAP alpha shows 48% amino acid sequence identity to the T-cell activation antigen CD26, a membrane-bound protein with dipeptidyl peptidase IV (DPPIV) activity; however, unlike FAP alpha, CD26 is widely expressed in normal tissues. Three catalytic domains shared by DPPIV homologues in different species and by other serine proteases are conserved in FAP alpha. Immunochemical analysis of COS-1 cells coexpressing FAP alpha and CD26 revealed that the two molecules form heteromeric cell surface complexes, suggesting that a previously identified FAP alpha-associated M(r) 105,000 protein of cultured fibroblasts and growth factor-stimulated melanocytes, FAP beta, is identical to CD26. In vivo coexpression of FAP alpha and CD26 is found in reactive fibroblasts of healing wounds but not in tumor stromal fibroblasts or sarcomas (FAP alpha +/CD26-). The putative serine protease activity of FAP alpha and its in vivo induction pattern may indicate a role for this molecule in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis.

Amino Acid Sequence↗
PubMed1999

Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

We developed an experimental approach with genetically engineered and encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible polymer AN69 for at least 90 days under in vitro and in vivo conditions because of their stable transfection with the gene for the 18-kDa form of the human basic fibroblast growth factor (hFGF-2). Furthermore, when transferred surgically into the vitreous cavity of 21-day-old Royal College of Surgeons rats, the microencapsulated hFGF-2-secreting fibroblasts provoked a local delay of photoreceptor cell degeneration, as seen at 45 days and 90 days after transplantation. This effect was limited to 2.08 mm2 (45 days) and 0.95 mm2 (90 days) of the retinal surface. In both untreated eyes and control globes with encapsulated hFGF-2-deficient fibroblasts, the rescued area (of at most 0.08 mm2) was significantly smaller at both time points. Although, in a few ocular globes, surgical trauma induced a reorganization of the retinal cytoarchitecture, neither microcapsule rejection nor hFGF-2-mediated tumor formation were detected in any treated eyes. These findings indicate that encapsulated fibroblasts secreting hFGF-2 or perhaps other agents can be applied as potential therapeutic tools to treat retinal dystrophies.

3T3 Cells↗
PubMed1993

Modulation of growth and function of human gingival fibroblasts by fibroblast-activating factor derived from Porphyromonas gingivalis W50.

The effect of a 24-kDa fibroblast-activating factor (FAF) isolated from outer membrane vesicles of Porphyromonas gingivalis W50 on the modulation of [3H]thymidine uptake and cell proliferation was examined in selected fibroblast and transformed cell lines. FAF enhanced the proliferation of human gingival fibroblasts, human skin fibroblasts, and human umbilical vein endothelial cells in subconfluent and confluent cells, suggesting that FAF might be functioning as a competence factor. The transformed cell lines, U-937 and HEp-2, were not responsive. FAF and several human-derived growth factors showed a synergistic effect on proliferation. [3H]proline and [3H]leucine were rapidly incorporated into fibroblasts in the presence of FAF; however, there was no selective induction of collagen synthesis. FAF was not active in the induction of interleukin-1 and interleukin-6. It is hypothesized that FAF from P. gingivalis functions as a growth factor for human fibroblasts but is without activity for transformed cells.

Antigens, Neoplasm↗
PubMed1995

Involvement of basic fibroblast growth factor in fibroblast-stimulatory serum activity of a patient with systemic lupus erythematosus and multiple dermatofibromas.

BACKGROUND: Multiple dermatofibromas (DFs) are often associated with systemic lupus erythematosus (SLE). An increased number of mast cells is observed in the upper portion or over the lesion of DF. OBJECTIVE: To investigate the role of the serum of a patient with multiple DFs, we examined its growth effects on fibroblasts. METHOD: 3H-Thymidine incorporation was used to examine the effects of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF and normal skin. RESULTS: The serum of the SLE patient with multiple DFs exhibited a stronger growth-stimulatory activity on normal and DF-derived fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or normal sera. The growth effects were inhibited in 40% by antiplatelet-derived-growth-factor antibody and almost completely inhibited by antibody against basic fibroblast growth factor. Cultured fibroblasts derived from the upper portion of the DF lesion, which included most of the numerous mast cells, demonstrated a higher level of 3H-thymidine uptake after stimulation of autologous serum compared to that from the mid and lower portions of DF. CONCLUSION: These results suggested the existence of various fibroblast growth factors derived from the mast cells in SLE patients with multiple DFs.

Adult↗
PubMed1995

Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro.

In patients with severe traumatic brain injury, the early healing of fractures is accompanied by hypertrophic callus formation or heterotopic ossifications, which might even result in ankylosis of the affected joints. Analysis of the sera of patients with traumatic brain injury revealed post-traumatic dynamic changes of basic fibroblast growth factor immunoreactivity, similar to those observed during fracture healing associated with enhanced osteogenesis. The aim of this study was to determine whether such changes in basic fibroblast growth factor concentrations could be related to the phenomenon of enhanced osteogenesis. Basic fibroblast growth factor immunoreactivity was determined (using an IEMA kit) in the sera of patients with traumatic brain injury and bone fractures (n = 8) and in the sera of patients with either traumatic brain injury alone (n = 10) or bone fractures alone (n = 7), and the effects of these sera on L929 fibroblast growth were analysed in vitro. The results did not prove a causative relationship between the changes of basic fibroblast growth factor immunoreactivity and in vitro growth promoting effects of the sera. However, it is apparent that, in addition to changes in the growth-promoting activity and basic fibroblast growth factor concentration of serum, other as yet unknown post-traumatic changes can cause enhanced osteogenesis.

Adolescent↗
PubMed2002

Differential effects of fibroblast growth factors on expression of genes of the plasminogen activator and insulin-like growth factor systems by human breast fibroblasts.

In breast stroma urokinase plasminogen activator (uPA) is predominantly expressed by fibroblasts located in the near vicinity of tumor cells, and fibroblast-derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the expression of uPA in these fibroblasts. To investigate a possible role for fibroblast growth factors (FGFs), we evaluated the expression of components of the PA system and the IGF system in normal and tumor-tissue-derived human breast fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1, FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA. Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall lagged behind but were longer-lasting. For FGF-4 an in between pattern was observed. Blocking transcription and translation demonstrated that a) both the FGF-1 and FGF-2 induced effects were the result of altered gene transcription or mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not depend on de novo protein synthesis during the first 24 h, but were triggered by proteins produced or made available thereafter. The data presented propose that of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive target for therapeutical strategies aimed at diminishing the contribution of stromal fibroblasts in the PA-directed breast tumor proteolysis.

Breast↗
PubMed2005

[Influence of basic fibroblast growth factors on the migration, proiferation of osteoblasts and periodontal ligament fibroblasts].

OBJECTIVE: In order to determine the influence of bFGF on the biological characteristics of osteoblasts and periodontal ligament cells, the author investigate the influence of bFGF on the migration, proliferation of osteoblasts and periodontal ligament fibroblasts between osteoblasts and fibroblasts. METHODS: The forth generation of osteoblasts and periodontal ligament fibroblast were obtained and the wounding model in vitro of them was founded. The cells were cultured in mediums with or without bFGF. Their migration and proliferation were observed and measured. RESULTS: Osteoblasts migrated faster than fibroblasts in common culture medium without bFGF and the periodontal ligament fibroblasts in culture medium with bFGF had higher migration rate than other groups. bFGF promoted the proliferation of both two kinds of cells. CONCLUSION: bFGF could accelerate periodontal fibroblasts' proliferation and migration.

Cell Proliferation↗
PubMed2004

Induction of RANKL expression and osteoclast maturation by the binding of fibroblast growth factor 2 to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by progressive joint destruction. The aim of this study was to clarify the relevance of RA synovial fibroblasts (RASFs) and fibroblast growth factor 2 (FGF-2), which is produced abundantly by RASFs, to the osteoclastogenesis and bone resorption in RA. METHODS: Synovial fibroblasts were prepared from the synovial tissues of 10 patients with active RA and 7 patients with osteoarthritis (OA). The expression of RANKL, intercellular adhesion molecule 1 (ICAM-1), FGF receptor 1 (FGFR-1), and heparan sulfate proteoglycan (HSPG) on synovial fibroblasts was measured by FACScan. Osteoclast formation in cocultures of RASFs and peripheral blood mononuclear cells (PBMCs) was evaluated by tartrate-resistant acid phosphatase staining and a pit-formation assay using dentin slices. RESULTS: FGF-2 induced the expression of both RANKL and ICAM-1 on RASFs more so than on OA synovial fibroblasts (OASFs). FGF-2-induced up-regulation of RANKL and ICAM-1 was inhibited by anti-FGF-2 antibody. Although FGFR-1 was equally expressed on RASFs and OASFs, HSPG was highly expressed on RASFs. Up-regulation of RANKL by FGF-2 on RASFs was diminished by the removal of heparan sulfate with heparitinase. Osteoclast formation from PBMCs induced by RASFs was inhibited by the addition of either heparitinase, anti-ICAM-1 antibody, anti-FGF-2 antibody, or osteoprotegerin. FGF-2-induced RANKL on RASFs and osteoclast formation were suppressed by an inhibitor of ERK. CONCLUSION: FGF-2 was transferred to FGFR-1 through binding to HSPG, which is characteristically expressed on RASFs, resulting in RANKL- and ICAM-1-mediated maturation of osteoclasts via ERK activation. Thus, we propose that FGF-2 not only augments the proliferation of RASFs, but also is involved in osteoclast maturation, which leads to bone destruction in RA.

Arthritis, Rheumatoid↗
PubMed1997

Control of fibroblast populated collagen lattice contraction by antibody targeted photolysis of fibroblasts.

BACKGROUND AND OBJECTIVE: Hypertrophic scarring and rigid scar contracture are disorders of wound healing for which there is presently no effective therapy. The dermal fibroblast plays a major role in scar fibrillogenesis and contracture. The objective of this study was to establish a selective and effective method to destroy fibroblasts. STUDY DESIGN/MATERIALS AND METHODS: An antifibroblast conjugate was synthesized by covalent attachment of the antifibroblast antibody PR2D3 to the photosensitizer Sn-chlorin e6. Fibroblasts were cultured in fibroblast-populated collagen lattices (FPCLs), incubated with the conjugate and exposed to light. The effect of the treatment on cell viability and the rate of contraction of the FPCL were assessed. RESULTS: The toxicity of antifibroblast conjugates increased with increasing conjugate concentration, light dose, and number of photosensitizers per antibody molecule, until nearly complete killing was achieved. The rate of lattice contraction after irradiation linearly correlated with the remaining viable fraction of fibroblasts. These conjugates were not cytotoxic to keratinocytes cultured on collagen lattices, and nonspecific conjugates could not cause significant fibroblast killing. Spatial selectivity was demonstrated using a light mask. CONCLUSIONS: Antibody-targeted photolysis is an effective and selective technique for controlling FPCL contraction in vitro and may have potential in vivo applications to modulate extracellular matrix remodeling by connective tissue cells.

Animals↗
PubMed1996

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗