Expression Of Fibroblast Growth Factor-5 Research Articles

Fibroblast growth factor 5 protects against spinal cord injury through activating AMPK pathway.

Excessive productions of inflammatory cytokines and free radicals are involved in spinal cord injury (SCI). Fibroblast growth factor 5 (FGF5) is associated with inflammatory response and oxidative damage, and we herein intend to determine its function in SCI. Lentivirus was instilled to overexpress or knockdown FGF5 expression in mice. Compound C or H89 2HCl were used to suppress AMP-activated protein kinase (AMPK) or protein kinase A (PKA), respectively. FGF5 level was significantly decreased during SCI. FGF5 overexpression mitigated, while FGF5 silence further facilitated inflammatory response, oxidative damage and SCI. Mechanically, FGF5 activated AMPK to attenuate SCI in a cAMP/PKA-dependent manner, while inhibiting AMPK or PKA with pharmacological methods significantly abolished the neuroprotective effects of FGF5 against SCI. More importantly, serum FGF5 level was decreased in SCI patients, and elevated serum FGF5 level often indicate better prognosis. Our study identifies FGF5 as an effective therapeutic and prognostic target for SCI.

MiR‑491‑3p functions as a tumor suppressor in non‑small cell lung cancer by targeting fibroblast growth factor 5

The present study aimed to identify the function of miR-491-3p in regulating non-small cell lung cancer (NSCLC). Tumor tissues and adjacent normal tissues were collected from 43 patients with NSCLC. A549 and H1299 cells were transfected with microRNA (miR)-491-3p mimic, mimic negative control (NC), miR-491-3p inhibitor, inhibitor NC, pcDNA3.1-FGF5 vector and control vector. Cell counting kit-8 assay and Edu experiments were performed to assess cell viability and proliferation. Matrigel experiment, wound healing assay and flow cytometric analysis were performed to explore cell invasion, migration and apoptosis, respectively. A dual-luciferase reporter experiment was performed to identify the relationship between miR-491-3p and fibroblast growth factor 5 (FGF5). In vivo study was conducted by using nude mice. The miR-491-3p and FGF5 protein expression levels were investigated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In NSCLC tumor tissues, miR-491-3p was downregulated and FGF5 was upregulated (P<0.01). Low miR-491-3p expression and high FGF5 mRNA expression was associated with poor outcomes in patients, including advanced TNM stage and lymph node metastasis (P<0.05). upregulation of miR-491-3p suppressed viability, proliferation, invasion and migration of NSCLC cells; however, it promoted apoptosis (P<0.01). FGF5 was a target gene for miR-491-3p. miR-491-3p directly inhibited FGF5 expression. upregulation of FGF5 significantly reversed the inhibitory effects of miR-491-3p on malignant phenotypes of NSCLC cells (P<0.01). miR-491-3p overexpression suppressed the in vivo growth of NSCLC. Thus, it was identified that miR-491-3p functions as a tumor suppressor in NSCLC by directly targeting FGF5.

Circ_0041732 regulates tumor properties of triple-negative breast cancer cells by the miR-149-5p/FGF5 pathway.

Triple-negative breast cancer (TNBC) is a subtype of breast cancers with a high recurrence and mortality. The important factors promoting the TNBC process have not been fully identified. In this research, the role of a TNBC-related circular RNA (circRNA), circ_0041732, was revealed in TNBC cell tumor properties. The expression levels of circ_0041732, microRNA-149-5p (miR-149-5p) and fibroblast growth factor 5 (FGF5) were detected by quantitative real-time polymerase chain reaction. The protein expression was determined by Western blot analysis or immunohistochemistry assay. Cell proliferation was detected by cell counting kit-8 and cell colony formation assays. Cell apoptosis was analyzed by flow cytometry and caspase-3 activity assays. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. Cell angiogenic capacity was investigated by a tube formation assay. The targeting relationship between miR-149-5p and circ_0041732 or FGF5 was identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of circ_0041732 knockdown on tumor formation were determined by an in vivo assay. Circ_0041732 and FGF5 expression were significantly upregulated, whereas miR-149-5p was downregulated in TNBC tissues and cells compared with normal breast tissues and cells, respectively. Circ_0041732 silencing inhibited TNBC cell proliferation, migration, invasion, and tube formation, but induced apoptosis. Additionally, circ_0041732 regulated TNBC cell tumor properties by binding to miR-149-5p. MiR-149-5p also modulated TNBC cell tumor properties by targeting FGF5. Furthermore, circ_0041732 knockdown hindered tumor formation in vivo. Circ_0041732 silencing suppressed TNBC cell tumor properties by decreasing FGF5 expression through miR-149-5p. This finding demonstrated that circ_0041732 had the potential as a therapeutic target for TNBC.

Vitamin A alleviates heat stress-induced damage to hair follicle development in Rex rabbits.

Rex rabbits are important fur rabbits. Heat stress severely reduces the fur quality of Rex rabbits. The aim of this study was to experimentally investigate the effect of dietary vitamin A (VA) addition on hair follicle development and related signal pathways in Rex rabbits under heat stress. In the experiment, 90 Rex rabbits were randomly divided into three groups: control group (20-25 °C, fed basic diet), heat stress group (30-34 °C, fed basic diet), and heat stress + VA group (20-25 °C, fed 12 000 IU/kg VA in addition to the basic diet). VA could significantly increase the hair follicle density (P < 0.01), hair length (P < 0.05), and the ratio of secondary to primary hair follicles (P < 0.05). In addition, VA could significantly inhibit the expression of BMP2, BMP4, FGF5, TGF-β1, and miR-214 in heat-stressed Rex rabbits and significantly increase the expression of noggin, IGF1, IGF1R, Wnt10b, CTNNB1, SHH, and miR-203 and the levels of Wnt10b and p-β-catenin; however, there was no significant effect of VA on the expression of EGF and miR-205. The dietary addition of VA can increase the hair follicle density and fur quality of heat-stressed Rex rabbits. Wnt10/β-catenin, insulin-like growth factor 1 (IGF1), fibroblast growth factor 5 (FGF5), noggin-BMP, and sonic hedgehog (SHH) signaling were associated with VA regulation under heat stress. It is possible that miR-205 and miR-194 contribute to the regulation of Wnt10/β-catenin and bone morphogenetic protein (BMP) signaling. © 2021 Society of Chemical Industry.

Fibroblast growth factor-5 promotes spermatogonial stem cell proliferation via ERK and AKT activation

BackgroundSertoli cells are the most important somatic cells contributing to the microenvironment (named niche) for spermatogonial stem cells (SSCs). They produce amounts of crucial growth factors and structure proteins that play essential roles in the complex processes of male SSCs survival, proliferation, and differentiation. It has been suggested that Sertoli cell abnormalities could result in spermatogenesis failure, eventually causing azoospermia in humans. However, to the end, the gene expression characteristics and protein functions of human Sertoli cells remained unknown. In this study, we aimed to evaluate the effect of fibroblast growth factor-5 (FGF5), a novel growth factor downregulated in Sertoli cells from Sertoli cell-only syndrome (SCOS) patients compared to Sertoli cells from obstructive azoospermia (OA) patients, on SSCs.MethodsWe compared the transcriptome between Sertoli cell from SCOS and OA patients. Then, we evaluated the expression of FGF5, a growth factor which is downregulated in SCOS Sertoli cells, in human primary cultured Sertoli cells and testicular tissue. Also, the proliferation effect of FGF5 in mice SSCs was detected using EDU assay and CCK-8 assay. To investigate the mechanism of FGF5, Phospho Explorer Array was performed. And the results were verified using Western blot assay.ResultsUsing RNA-Seq, we found 308 differentially expressed genes (DEGs) between Sertoli cells from SCOS and OA patients. We noted and verified that the expression of fibroblast growth factor-5 (FGF5) was higher in Sertoli cells of OA patients than that of SCOS patients at both transcriptional and translational levels. Proliferation assays showed that rFGF5 enhanced the proliferation of mouse SSCs line C18-4 in a time- and dose-dependent manner. Moreover, we demonstrated that ERK and AKT were activated and the expression of Cyclin A2 and Cyclin E1 was enhanced by rFGF5.ConclusionThe distinct RNA profiles between Sertoli cells from SCOS and OA patients were identified using RNA-Seq. Also, FGF5, a growth factor that downregulated in SCOS Sertoli cells, could promote SSCs proliferation via ERK and AKT activation.

Downregulation of fibroblast growth factor 5 inhibits cell growth and invasion of human nonsmall-cell lung cancer cells.

The morbidity and mortality rates of nonsmall-cell lung cancer (NSCLC) have increased in recent years. We aimed to explore the biological role of fibroblast growth factor 5 (FGF5) in NSCLC. We first established that the expression of FGF5 was increased in NSCLC tissues compared with the normal adjacent tissues. The expression of FGF5 was also increased in NSCLC cell lines. The effect of FGF5 silencing on cell proliferation, cell cycle, apoptosis, migration, and invasion of H661 and CALU1 cells was then examined. Downregulation of FGF5 significantly inhibited cell proliferation and induced G1 phase cell cycle arrest compared with the negative control small interfering (siNC) groups. Cell apoptosis was promoted by siFGF5 treatment. Cell migration and invasion of H661 and CALU1 cells with siFGF5 transfection were markedly diminished compared with the siNC groups. In addition, migration and invasion-associated proteins (E-cadherin, matrix metalloproteinase-2 [MMP-2], and MMP-9) and epithelial mesenchymal transition markers (N-cadherin, vimentin, snail, and slug) were also regulated by FGF5 siRNA treatment. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) cell cycle and vascular endothelial growth factor (VEGF) pathways were correlated with FGF5 expression, which was further confirmed in NSCLC cells by Western blot analysis. Our results indicated that FGF5 silencing suppressed cell growth and invasion via regulation of the cell cycle and VEGF pathways. Therefore, FGF5 may serve as a promising therapeutic strategy for NSCLC.

Expression of Fibroblast Growth Factor 5 (FGF5) and Its Influence on Survival of Breast Cancer Patients.

BackgroundThe clinical outcome of patients with breast cancer (BC) remains poor.Material/MethodsWe analyzed BC microarray studies GSE37751, GSE7390, and GSE21653 to investigate the expression of FGF5 gene between BC patients and their normal counterparts and the relationship between FGF5 expression and age, tumor size, histopathological grading, estrogen receptors, clinical risk group according to St Gallen criteria, clinical risk group according to NPI criteria, clinical risk group according to Veridex signature, distant metastasis-free survival (DMFS), time to distant metastasis (TDM), disease-free survival (DFS), and overall survival (OS) of BC patients. Gene set enrichment analysis (GSEA) was used to investigate the exact mechanisms.ResultsFGF5 expression was significantly upregulated in BC patients relative to that in normal controls (P<0.0001). BC patients in the FGF5 low-expression group were correlated with better clinical characteristics, including tumor size, histopathological grading, estrogen receptors, clinical risk group according to St Gallen criteria, NPI criteria and Veridex signature, DMFS, TDM, and DFS compared with those in the FGF5 high-expression cohort. The result of GSEA indicated that FGF5 inhibits the proliferation of BC cells via ultraviolet response and TGF-β signaling. Quantitative PCR verified that FGF5 was overexpressed in patients with BC.ConclusionsOur results suggest that FGF5 is an independent protective factor for BC patients.

Ectopic expression of FGF5s induces wool growth in Chinese merino sheep

Fibroblast growth factor 5 (FGF5) has been recognized as an inhibitor to cease animal hair growth, while in contrary, FGF5 short alternative transcript (FGF5s) can induce hair growth by antagonizing FGF5 function. To investigate the role of FGF5s in wool growth in Chinese Merino sheep, we generated transgenic sheep of ectopic expression of FGF5s by injection of recombinant lentivirus into zygote. Totally 20 transgenic sheep were obtained and 12 were alive after birth. Characterization of the transgene revealed that the transgenic sheep showed variety of integrant, ranged from 2 to 11 copies of transgene. The ectopic expression of FGF5s was observed in all transgenic sheep. Further study on the effect of ectopic expression of FGF5s revealed that the wool length of transgenic sheep were significantly longer than that of non-transgenic control, with 9.17cm of transgenic lambs versus 7.58cm of control animals. Notably, besides the increase of wool length, the yearling greasy fleece weight was also concordantly greater than that of wild-type (p<0.01), with 3.22kg of transgenic sheep versus 2.17kg of control lambs (p<0.01) in average. Our results suggested that overexpression of FGF5s could stimulate wool growth and resulted in increase of wool length and greasy wool weight.

Role of Fibroblast Growth Factor-5 on the Proliferation of Human Tonsil-Derived Mesenchymal Stem Cells.

Human mesenchymal stem cells (MSCs) are a promising tool for therapeutic applications in cell-based therapy and regenerative medicine, and MSCs from the human palatine tonsils have recently been used as a new tissue source. However, the understanding of the proliferation and differentiation capacity of tonsil-derived MSCs (T-MSCs) is limited. In this study, we compared the proliferative potential of T-MSCs with those of bone marrow MSCs (BM-MSCs) and adipose tissue-derived MSCs (A-MSCs). Additionally, we investigated the underlying mechanism of T-MSC function. We showed that T-MSCs proliferated faster than A-MSCs and BM-MSCs in methylthiazolyl diphenyl-tetrazolium (MTT) assays, cell count assays, and cell cycle distribution analyses. DNA microarray and real-time PCR analyses revealed that the expression of fibroblast growth factor-5 (FGF5) was significantly elevated in T-MSCs compared with those in A-MSCs and BM-MSCs. Cell growth curves showed a difference in cell growth between untreated cells and siFGF5-treated T-MSCs. The administration of recombinant human FGF5 (rhFGF5) to the cells transfected with siFGF5 led to a significant increase in the proliferation rates. The administration of rhFGF5 to T-MSCs led to an increase in the levels of phosphorylated ERK1/2. However, treatment with siFGF5 resulted in an overall decrease in the level of phosphorylated ERK1/2. The osteogenic differentiation of T-MSCs was reduced following siFGF5 transfection, and it recovered to near-normal levels when rhFGF5 was added. These findings indicate that T-MSCs show significantly higher proliferative potential compared with those of BM-MSCs and A-MSCs. FGF5 facilitates cell proliferation through ERK1/2 activation, and it influences the osteogenic differentiation of T-MSCs.

The Success of Thread-embedding Therapy in Generating Hair Re-growth in Mice Points to Its Possibly Having a Similar Effect in Humans.

Objectives:Recently, thread-embedding therapy (TET) has been widely applied in Korean medicine for cosmetic purposes such as reducing skin wrinkles. An inserted thread was reported to have induced continuous stimulation, followed by support for connective tissue regeneration. However, the potential role of TET in hairgrowth has not yet been reported.Methods:We designed this study to evaluate whether TET has a hair-growth-promoting effect. C57 black 6 (C57BL/6) mice were divided into three groups: normal saline-treated, minoxidil-treated, and thread-embedded groups. Normal saline or 5% minoxidil was topically sprayed on the dorsal skin of the mice once a day for 16 days. Medical threads were embedded into the dorsal skin of the mice in a single application. Hair growth activity was evaluated by using dermoscopic and microscopic observations. Sections of the dorsal skin were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7), and fibroblast growth factor-5 (FGF-5) were detected by using immunohistochemical staining. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was adopted to measure the messenger RNA (mRNA) expressions of FGF-7 and FGF-5.Results:TET enhanced anagen development in the hair follicles of C57BL/6 mice. The expressions of BrdU and PCNA, both of which imply active cellular proliferation, were increased by using TET. Moreover, TET increased the expression of FGF-7, an anagen-inducing growth factor, while decreasing the expression of FGF-5, an anagen-cessation growth factor, both at the protein and the mRNA levels.Conclusion:TET enhanced hair re-growth in C57BL/6 mice. TET regulated the expressions of anagen-associated growth factors and activated the proliferation of hair follicular cells in depilated skin lesions. Considering its long-lasting effect, TET may be a good alternative therapeutic for the treatment of alopecia.

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC. miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo. miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis. These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.

Sox2 Is an Androgen Receptor-Repressed Gene That Promotes Castration-Resistant Prostate Cancer

Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

Cloning, expression analysis and RNA interference of &lt;I&gt;FGF5&lt;/I&gt; gene in sheep

The cDNA of fibroblast growth factor 5 (FGF5) gene in sheep was cloned, and the nucleotides sequence homology of FGF5 was compared with other six mammal. In addition, the expression of FGF5 in different tissues was analysed. Gene FGF5 was then recombined into prokaryotic expression vector (pGEX-4T-2) and RNA interference vector (pSilencer 5.1 H1) to study its expression in fibroblast cell lines. Results showed that the open reading frame (ORF) of cDNA in sheep consisted of 813 nucleotide acids encoding 270 amino acids, with the molecular mass of 29.58 kDa and theoretical pI of 10.59. The amino acids sequence of FGF5 gene in sheep shared high identity with those in cow, human, mouse, rat, dog, cat and rabbit. In addition, analysis on tissue expression showed that FGF5 expressed in skin, heart, kidney, liver, pancreas, spleen, lung, and small intestine, especially presenting high levels in skin. The expression of FGF5 in E. coli was induced with IPTG, which produced a protein band with the expected size of 56 kDa on SDS-PAGE, while the expression of FGF5 in sheep fibroblast cell line was knocked down remarkably with the help of integrated RNAi vector.

Axon-Schwann cell interactions regulate the expression of fibroblast growth factor-5 (FGF-5).

We screened for genes whose expression is significantly up- or downregulated during Wallerian degeneration in adult rat sciatic nerve with cDNA arrays. Fibroblast growth factor-5 (FGF-5) mRNA seemed to be induced. This was confirmed by northern blotting and in situ hybridization, as well as Western blotting for FGF-5 in axotomized nerve. Axon-Schwann cell interactions decreased the steady-state level of FGF-5 mRNA in regenerating sciatic nerves, and forskolin diminished its expression in cultured Schwann cells. We conclude that denervated Schwann cells synthesize FGF-5, which is a secreted, neuronotrophic member of the FGF family.

Fibroblast growth factor-5 is expressed in Schwann cells and is not essential for motoneurone survival.

Fibroblast growth factor-5 (FGF-5) is a putative target-derived survival factor for motoneurones as it is concentrated in the synaptic portions of skeletal muscles and because it promotes the survival of embryonic motoneurones in vitro. A variety of experimental approaches have been used to examine this possibility. The expression of FGF-5 in the neuromuscular system was analysed using the reverse transcription-polymerase chain reaction (RT-PCR). Both splice variants of FGF-5 were detected in adult rat skeletal muscle, sciatic nerve, and spinal cord. The expression of FGF-5 in skeletal muscle was up-regulated after denervation. At first sight this appears to be consistent with FGF-5 being a target-derived factor. However, FGF-5 protein was detected in Schwann cells, macrophages, vascular smooth muscle and endothelial cells, but not in muscle fibres. The absence of FGF-5 in muscle fibres was confirmed by RT-PCR examination of isolated muscle fibres. Furthermore, FGF-5 protein was also not detected in denervated fibres, as would be expected for a neuronal survival factor. Denervation did however lead to up-regulation of FGF-5 in the Schwann cells of the distal nerve trunk. This may indicate that FGF-5 is either an autocrine regulator of Schwann cells or a Schwann cell-derived neurotrophic factor. The latter appears not to be the case for two reasons. First, the double-ligation technique was used to show that endogenous FGF-5 is not transported in motor axons. Second, stereological estimates of the number of motoneurones in an FGF-5 null mutant (Angora) mouse failed to reveal any loss of motoneurones. Collectively these experiments suggest that FGF-5 is not a physiological regulator of motoneurones, and therefore raise the possibility that it is an autocrine regulator of Schwann cells.

Distribution of fibroblast growth factor-5 in rat hypothalamus, and its possible role as a regulator of feeding behaviour.

We previously reported that a transcript of fibroblast growth factor-5 (FGF-5) was more abundant in the brain of postnatal and adult mice than in the embryonic brain. This suggested that FGF-5 plays some role in the mature brain. Here, we have investigated the spatiotemporal expression and function of FGF-5 in the adult rat hypothalamus with the emphasis on feeding behaviour. In situ hybridization experiments demonstrated that, in both adequately fed and fasted (20 h) rats, FGF-5 transcripts were present within several nuclei in the hypothalamus (viz. the magnocellular part of the paraventricular nucleus, supraoptic nucleus, arcuate nucleus, median eminence, and ventromedial hypothalamic nucleus), but not in the lateral hypothalamic area. Quantitative detection of FGF-5 mRNA in the hypothalamus (especially in the paraventricular nucleus) indicated that food deprivation (20 h) reduced the expression of this gene to almost one-half of that seen in the control (fed) rats. The expression recovered to the control level after 1 h re-feeding, and this recovery persisted for several hours. Furthermore, FGF-5, when infused into the third ventricle, consistently reduced food intake, water intake and body weight gain, all in a dose-dependent manner. These results suggest that FGF-5 in the hypothalamus acts as a physiological regulator of feeding behaviour, and that its decreased expression during food deprivation may be important in stimulating appetite.

Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements of the pancreas in chronic pancreatitis

Background—Fibroblast growth factor 5 (FGF-5) belongs to a group of mitogenic and angiogenic heparin binding growth factors but its potential role in chronic inflammatory conditions is not known.Aims—To compare FGF-5...

Biosynthesis of Human Fibroblast Growth Factor-5

We have analyzed the biosynthesis of human fibroblast growth factor-5 (FGF-5) at the translational and posttranslational levels. FGF-5 RNA synthesized in vitro can be translated in rabbit reticulocyte lysates to yield a 29,500-Da protein, which is consistent with the molecular weight predicted from the coding sequence. The efficiency of FGF-5 translation is dramatically enhanced if an upstream open reading frame (ORF-1) in the RNA is deleted or if both AUG codons in ORF-1 are destroyed by point mutations, while partial enhancement is achieved by individual mutation of either ORF-1 AUG codon. These data suggest that FGF-5 synthesis requires the scanning of ribosomes past the two ORF-1 AUG codons. The introduction of these ORF-1 mutations into a eukaryotic FGF-5 expression vector increases its capacity to transform mouse NIH 3T3 cells up to 50-fold upon transfection. FGF-5 is secreted from transfected 3T3 cells and from human tumor cells as glycoproteins containing heterogeneous amounts of sialic acid. Glycosidase treatments suggest that the growth factor bears both N-linked and O-linked sugars.

Biosynthesis of human fibroblast growth factor-5.

We have analyzed the biosynthesis of human fibroblast growth factor-5 (FGF-5) at the translational and posttranslational levels. FGF-5 RNA synthesized in vitro can be translated in rabbit reticulocyte lysates to yield a 29,500-Da protein, which is consistent with the molecular weight predicted from the coding sequence. The efficiency of FGF-5 translation is dramatically enhanced if an upstream open reading frame (ORF-1) in the RNA is deleted or if both AUG codons in ORF-1 are destroyed by point mutations, while partial enhancement is achieved by individual mutation of either ORF-1 AUG codon. These data suggest that FGF-5 synthesis requires the scanning of ribosomes past the two ORF-1 AUG codons. The introduction of these ORF-1 mutations into a eukaryotic FGF-5 expression vector increases its capacity to transform mouse NIH 3T3 cells up to 50-fold upon transfection. FGF-5 is secreted from transfected 3T3 cells and from human tumor cells as glycoproteins containing heterogeneous amounts of sialic acid. Glycosidase treatments suggest that the growth factor bears both N-linked and O-linked sugars.

Expression of the murine fibroblast growth factor 5 gene in the adult central nervous system.

The murine homolog of the fibroblast growth factor-5 (FGF-5) gene has been cloned, and the sequence of the gene's three exons has been determined. The murine gene and the previously isolated human FGF-5 gene are substantially homologous within the coding sequences and in upstream sequences, which contain an additional open reading frame. We have used a portion of the murine gene as probe to detect FGF-5 RNA in adult mouse tissues by both Northern blot and in situ hybridization methods. FGF-5 RNA is present at low levels in widely distributed areas of the central nervous system. Several loci of FGF-5 expression could be localized by in situ hybridization and include portions of the cerebral cortex, hippocampus, and thalamus. Neuronal expression accounts for at least some of the FGF-5 RNA synthesized in the central nervous system.