Fibroblast Growth Factor 10 Gene Research Articles

Recombinant human fibroblast growth factor 7 obtained from stable Chinese hamster ovary cells enhances wound healing.

Although fibroblast growth factor 7 (FGF7) is known to promote wound healing, its mass production poses several challenges and very few studies have assessed the feasibility of producing FGF7 in cell lines such as Chinese hamster ovary (CHO) cells. Therefore, this study sought to produce recombinant FGF7 in large quantities and evaluate its wound healing effect. To this end, the FGF7 gene was transfected into CHO cells and FGF7 production was optimized. The wound healing efficacy of N-glycosylated FGF7 was evaluated in animals on days 7 and 14 post-treatment using collagen patches (CPs), FGF7-only, and CP with FGF7 (CP+FGF7), whereas an untreated group was used as the control. Wound healing was most effective in the CP+FGF7 group. Particularly, on day 7 post-exposure, the CP+FGF7 and FGF7-only groups exhibited the highest expression of hydroxyproline, fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor. Epidermalization in H&E staining showed the same order of healing as hydroxyproline content. Additionally, the CP+FGF7 and FGF7-only group exhibited more notable blood vessel formation on days 7 and 14. In conclusion, the prepared FGF7 was effective in promoting wound healing and CHO cells can be a reliable platform for the mass production of FGF7.

RNA-Seq explores the functional role of the fibroblast growth factor 10 gene in bovine adipocytes differentiation.

The present study was executed to explore the molecular mechanism of fibroblast growth factor 10 (FGF10) gene in bovine adipogenesis. The bovine FGF10 gene was overexpressed through Ad-FGF10 or inhibited through siFGF10 and their negative control (NC) in bovine adipocytes, and the multiplicity of infection, transfection efficiency, interference efficiency were evaluated through quantitative real-time polymerase chain reaction, western blotting and fluorescence microscopy. The lipid droplets, triglycerides (TG) content and the expression levels of adipogenic marker genes were measured during preadipocytes differentiation. The differentially expressed genes were explored through deep RNA sequencing. The highest mRNA level was found in omasum, subcutaneous fat, and intramuscular fat. Moreover, the highest mRNA level was found in adipocytes at day 4 of differentiation. The results of red-oil o staining showed that overexpression (Ad-FGF10) of the FGF10 gene significantly (p<0.05) reduced the lipid droplets and TG content, and their downregulation (siFGF10) increased the measurement of lipid droplets and TG in differentiated bovine adipocytes. Furthermore, the overexpression of the FGF10 gene down regulated the mRNA levels of adipogenic marker genes such as CCAAT enhancer binding protein alpha (C/EBPα), fatty acid binding protein (FABP4), peroxisome proliferator-activated receptor-γ (PPARγ), lipoprotein lipase (LPL), and Fas cell surface death receptor (FAS), similarly, down-regulation of the FGF10 gene enriched the mRNA levels of C/EBPα, PPARγ, FABP4, and LPL genes (p<0.01). Additionally, the protein levels of PPARγ and FABP4 were reduced (p<0.05) in adipocytes infected with Ad-FGF10 gene and enriched in adipocytes transfected with siFGF10. Moreover, a total of 1,774 differentially expressed genes (DEGs) including 157 up regulated and 1,617 down regulated genes were explored in adipocytes infected with Ad-FGF10 or Ad-NC through deep RNA-sequencing. The top Kyoto encyclopedia of genes and genomes pathways regulated through DEGs were the PPAR signaling pathway, cell cycle, base excision repair, DNA replication, apoptosis, and regulation of lipolysis in adipocytes. Therefore, we can conclude that the FGF10 gene is a negative regulator of bovine adipogenesis and could be used as a candidate gene in marker-assisted selection.

A novel 22-bp InDel within FGF7 gene is significantly associated with growth traits in goat

Fibroblast growth factor 7 (FGF7) is involved in lipid metabolism, which is considered as a candidate gene with close relation with muscle development by eGWAs and RNA-Seq analyses. To date, limited research has been conducted on the relationship between FGF7 gene and growth traits. The main objective of this work was to further investigate the association between novel InDel within FGF7 gene and growth traits in goat. Herein, FGF7 mRNA expression levels were investigated in various Fuqing goat tissues. We found that FGF7 gene was expressed in six adult goat tissues with the highest mRNA levels in adipose tissue. This result suggested that FGF7 gene might play a critical role in fat deposition. We also detected potential polymorphisms in Fuqing, Nubian and Jianyang Daer breeds. A 22-bp InDel polymorphism in FGF7 gene was detected in 396 goats and the three genotypes were designated as II, ID, and DD. Correlation analysis revealed that InDel polymorphism was significantly associated with growth traits (P < 0.05). Goats with genotypes ID and/or II had superior growth traits compared to those with genotype DD. In summary, our findings suggested that the 22-bp InDel within FGF7 gene could act as a molecular marker to improve the growth traits of goats in breeding programs.

Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children.

Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands.Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking. We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing. All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.

The role of FGF9-mediated TGF-β1/Smad signaling in enamel hypoplasia induced by exposure to fluoride and SO2 in rats

Many geographical areas of the world are polluted by both fluoride and sulfur dioxide (SO2). However, the effects of simultaneous exposure to fluoride and SO2 on teeth are unknown. Fibroblast growth factor-9 (FGF9) and transforming growth factor-β1 (TGF-β1) are key signaling molecules in enamel development. The purpose of the study was to explore the effects of co-exposure to fluoride and sulfur dioxide on enamel and to investigate the role and mechanism of FGF9 and TGF-β1. First, sodium fluoride (NaF) and SO2 derivatives were used to construct rat models and evaluate the enamel development of rats. Then, TGF-β1 (cytokine) treatment, SIS3 (inhibitor) treatment and FGF9 gene knockdown were used to explore the mechanism of enamel damage in vitro. The results showed that enamel column crystals in the exposed group were characterized by enamel hypoplasia, as indicated by alterations such as disarrangement of enamel column crystals, space widening and breakage. Ameloblasts also showed pathological changes such as ribosome loss, mitochondrial swelling, nuclear fragmentation and chromatin aggregation. The protein expression of FGF9 was higher and the protein expression of AMBN, TGF-β1 and p-Smad2/3 protein was lower in the groups treated with fluoride and SO2 individually or in combination compared with the control group. Further studies showed that TGF-β1 significantly upregulated p-Smad2/3 and AMBN protein expression and reduced the inhibitory effects of fluoride and SO2; furthermore, SISI blocked the effect of TGF-β1. In addition, knockdown of FGF9 upregulated TGF-β1 protein expression, further activated Smad2/3 phosphorylation, eliminated the inhibitory effects of fluoride and SO2, and increased the protein expression of AMBN. In brief, the study confirms that co-exposure to fluoride and SO2 can result in enamel hypoplasia in rats and indicates that the underlying mechanism may be closely related to the effect of FGF9 on enamel matrix protein secretion through inhibition of the TGF-β1/Smad signaling pathway.

Craniofacial anomalies in a murine model of heterozygous fibroblast growth factor 10 gene mutation.

Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo-Auriculo-Dento-Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/- ) mutation at skeletal maturity. Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/- mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro-computed tomography. Landmark-based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/- mice (P < .05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P > .05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. The FGF10+/- mutation was associated with craniomaxillary skeletal hypoplasia thatprobably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, theskeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion.

P40 Dry eyes and a dry mouth: is it Sjögren’s syndrome?

P40 Dry eyes and a dry mouth: is it Sjögren’s syndrome?

Genetic and functional analyses of TBX4 reveal novel mechanisms underlying pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is a fatal disease, with approximately 10% of cases associated with genetic variants. Recent genetic studies have reported pathogenic variants in the TBX4 gene in patients with PAH, especially in patients with childhood-onset of the disease, but the pathogenesis of PAH caused by TBX4 variant has not been fully uncovered. MethodsWe analysed the TBX4 gene in 75 Japanese patients with sporadic or familial PAH using a PCR-based bidirectional sequencing method. Detected variants were evaluated using in silico analyses as well as in vitro analyses including luciferase assay, immunocytochemistry and chromatin immunoprecipitation (ChIP) whether they have altered function. We also analysed the function of TBX4 using mouse embryonic lung explants with inhibition of Tbx4 expression. ResultsPutative pathogenic variants were detected in three cases (4.0%). Our in vitro functional analyses revealed that TBX4 directly regulates the transcriptional activity of fibroblast growth factor 10 (FGF10), whereas the identified TBX4 variant proteins failed to activate the FGF10 gene because of disruption of nuclear localisation signal or poor DNA-binding affinity. Furthermore, ex vivo inhibition of Tbx4 resulted in insufficiency of lung morphogenesis along with specific downregulation of Tie2 and Kruppel-like factor 4 expression. ConclusionOur results implicate variants in TBX4 as a genetic cause of PAH in a subset of the Japanese population. Variants in TBX4 may lead to PAH through insufficient lung morphogenesis by disrupting the TBX4-mediated direct regulation of FGF10 signalling and pulmonary vascular endothelial dysfunction involving PAH-related molecules.

Bioinformatics and genetic variants analysis of FGF10 gene promoter with their association at carcass quality and body measurement traits in Qinchuan beef cattle

The fibroblast growth factor 10 (FGF10) gene regulates adipogenesis and myogensis. In this study, sequencing of FGF10 prompter region identified three SNPs at loci g.78G > A, g.116C > T and g.201A > T. Each SNP yields three genotypes as GG, GA and AA at loci g.78G > A, CC, CT and TT at loci g.116C > T and AA, AT and TT at loci g.201A > T. Allelic and genotypic frequencies of all three SNPs deviated from the Hardy–Weinberg equilibrium (HWE) (P < 0.05) and were found highly polymorphic as PIC (0.25 < PIC < 0.50). Moreover, we found highest LD (D′/γ2) between SNP2 and SNP3 (0.989/0.909), followed by SNP1 and SNP3 (0.944/0.796). Moreover, three variants of FGF10 gene promoter exhibited significant (P < 0.05) association with body measurement and carcass quality traits in Qinchuan beef cattle. At loci g.78G > A, the genotype GG showed significantly (P < 0.01) larger body length (BL), rump length (RL), chest depth (CD), chest circumference (CC) and ultrasound loin area (ULA). The genotype TC at loci g.116C > T showed significantly (P < 0.01 and 0.05) larger body measurement and intramuscular fat, and ultrasound loin area (ULA). In addition to that, at loci g.201A > T, genotype TT showed significantly (P < 0.01 and P < 0.05) larger body length (BL), rump length (RL), hip width (HW), chest circumference (CC) and ultrasound loin area (ULA). Additionally, screening of promoter sequence of FGF10 gene explored loss of four TFs binding sites (KLF3, ZNF37α, GLIS2 and BCL11A) at g.116C > T because of SNP2. However, a single TF binding site was lost at g.202A > T due to SNP3. Interestingly, none of TF binding site was lost at g.78G > A in SNP1; however, one new TF binding site was gained at this location due to SNP1. These findings conclude that genotype GG, TC and TT could be used as genetic markers of FGF10 gene for body measurement and carcass quality traits in Qinchuan beef cattle.

The Expression, Morphology, and Clinical Characteristics of Fibroblast Growth Factor-10 in Breast Cancer

Background: Fibroblast growth factor-10 (FGF-10) is a member of a superfamily with characteristics of epithelial cell proliferation and embryonic development and is assumed to have a role in a phenomenon called the epithelial-mesenchymal transition (EMT). The previous study has revealed the critical role of FGF-10 in type III EMT in breast cancer cell lines. The mentioned finding, demonstrates the possible role of this factor in type III EMT in cancers with different origins such as breast. The present study investigated the expression of FGF-10 as a mitotic-inducing growth factor, normally has a low expression in breast tissues amongst breast cancer patients. Materials and Methods: 67 breast cancer tissues and 8 normal breast tissues were randomly selected from the Iran national tumor bank. The FGF-10 gene expression analysis was performed after the RNA expression using the real-time RTPCR, which was followed by the Student’s t-test statistical analysis. Results: The findings revealed that the relative expression of FGF-10 was elevated in tumor tissues as compared with normal breast tissues, and the higher expression had a direct correlation with the progression of clinical and pathologic staging. The expression was also significantly higher in triple-negative breast cancer and p53 null tissues. Conclusion: Taken together, it is suggested that, although in some variables it was not significant but generally the invasion and migration in tumor tissues are the same as in-vitro analysis as indicated before, and the expression has a direct relationship with the molecular presentation and clinical -pathological progression.

MicroRNA-155-5p promotes cell proliferation and invasion in lung squamous cell carcinoma through negative regulation of fibroblast growth factor 9 expression.

BackgroundNon-small cell lung cancer (NSCLC) ranks first for mortality among all malignancies. Squamous cell carcinoma (SCC) is one of the main types of NSCLC. Previous studies have found that fibroblast growth factor 9 (FGF9) is closely related to lung SCC via different molecular regulatory mechanisms. This study aimed to explore the relationship between microRNA-155-5p (miR-155-5p) and FGF9 gene expression and their effects on the proliferation and invasion of lung SCC through experiments, in order to provide theoretical basis for overcoming this disease.MethodsFluorescence quantitative polymerase chain reaction was employed for the detection miR-155-5p and FGF9 expression in lung SCC tissues (n=40) and the corresponding adjacent normal tissues. The expression of FGF9 in the cancerous and adjacent tissues was detected by western blot. Transwell assay used to verify the effect of miR-155-5p on FGF-induced invasion and migration. Finally, subcutaneous tumor formation experiments in nude mice were used to verify how miR-155-5p and FGF9 affect the proliferative ability of lung SCC cells.ResultsThe results of fluorescence quantitative PCR revealed that miR-155-5p and FGF9 were expressed at high and low levels, respectively, in lung SCC tissue samples relative to normal adjacent tissue samples. Western blot analysis of 6 lung SCC tissue samples revealed a significantly reduced level of FGF9. Correlation analysis uncovered that miR-155-5p and FGF9 share a significant negative correlation in lung SCC. At the messenger RNA and protein levels miR-155-5p could negatively regulate the expression of FGF9. Bioinformatics and dual luciferase reporter assay results confirmed FGF9 to be a downstream regulatory gene targeted by miR-155-5p. Our in vitro and in vivo results demonstrated that FGF9 overexpression exerted a significant inhibitory effect on miR-155-5p’s ability to promote lung cancer cell growth, invasion, and proliferation.ConclusionsOur results show that miR-155-5p, as an oncogene, negative regulates FGF9 expression to promote SCC occurrence and development in the lungs.

Mechanism of FGF7 gene silencing in regulating viability, apoptosis, invasion of retinoblastoma cell line HXO-Rb44 and angiogenesis.

To explore the mechanism of fibroblast growth factor 7 (FGF7) gene silencing in regulating viability, apoptosis, invasion of retinoblastoma (RB) cell line HXO-Rb44 and angiogenesis. Human normal retinal vascular endothelial cells ACBRI-181 was set as the normal group. The cultured RB cell lines HXO-Rb44 were divided into three groups: the blank group (without plasmid transfection), negative control group (transfection of FGF7 plasmid), and the si-FGF7 group (transfection of FGF7 siRNA plasmid). Quantitative Real Time-Polymerase Chain Reaction and Western blot were used to measure the mRNA and protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), and proliferating cell nuclear antigen (PCNA) in each group. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell invasion assay, and flow cytometry were used, respectively, to assess cell viability, invasive capability, and cell apoptosis in each group. The mRNA and protein expression of FGF7, Bcl-2, VEGF, bFGF, Ang-2, and PCNA were significantly decreased, and the mRNA and protein expression of Bax were significantly increased in the si-FGF7 group than in the blank group (all p<0.05). Compared with the blank group, the si-FGF7 group had significantly decreased cells invasive capability, cell viability at 48 h and 72 h and proliferation, and significantly increased apoptosis rate (all p<0.05). FGF7 gene silencing can inhibit the viability and invasion of RB cells and the expression of angiogenesis-related factors and can promote RB apoptosis.

Congenital diaphragmatic hernia as a potential target for transamniotic stem cell therapy

PurposeWe sought to determine whether TRASCET could impact congenital diaphragmatic hernia (CDH). MethodsTwelve pregnant dams received Nitrofen on gestational day 9.5 (E9; term = 22 days) to induce fetal CDH. Fetuses were divided into three groups: untreated (n = 31) and two groups receiving volume-matched intraamniotic injections of either saline (n = 37) or a suspension of 2 × 106 cells/mL of amniotic fluid-derived mesenchymal stem cells (afMSCs; n = 65) on E17. Animals were euthanized at term. Expression of fibroblast growth factor-10 (FGF-10), vascular endothelial growth factor-A (VEGF-A), and surfactant protein-C (SPC) was quantified by qRT-PCR. Statistical analysis was by the Mann–Whitney U test with Bonferroni adjusted criterion (p ≤ 0.01). ResultsAmong survivors with CDH (n = 27/133), the TRASCET group showed significant downregulation of FGF-10 and VEGF-A gene expressions compared to the untreated (p < 0.001 for both) and saline groups (p = 0.005 and p = 0.004, respectively). SPC expression was higher in the TRASCET group compared to the untreated group (p = 0.01), but not the saline group (p = 0.043). Lung laterality had minimal impact on these comparisons. ConclusionsTransamniotic stem cell therapy affects select processes of lung development in experimental congenital diaphragmatic hernia. Further scrutiny into this novel therapy as a potential component of the prenatal management of this disease is warranted. Level of evidenceN/A (animal and laboratory study).

Fibroblast growth factor-10 and epithelial-mesenchymal transition in colorectal cancer.

As an inducer of epithelial-mesenchymal transition (EMT), fibroblast growth factor-10 (FGF-10) has a role in cell proliferation and differentiation in the embryo in addition to invasion and metastasis during carcinogenesis. In this study, we aimed to investigate the FGF-10 gene expression in tumor tissues based on the pathological feature of tumor related to EMT and metastasis. 62 tumors were obtained from 62 colorectal cancer patients during surgery. The pathological characteristics of the patients were carefully collected and classified by Iran National Tumor Bank. To quantify FGF-10 gene expression, RNA extraction, reverse transcription-PCR and real-time PCR were respectively performed. In addition, three colorectal cancer cell lines including LS174T, SW-948 and SW-480 were collected and cultured for further molecular analysis. Consequently, FGF-10 gene expression showed increased expression level in LS174T and SW-948 while it displayed decreased level in SW-480. Considering the tumor samples, we found an upregulation of FGF-10 gene expression in 52.1 % of all tumors in stage III and only in 9.09 % of all tumors in stage I. Also, there were an upregulation of FGF-10 gene expression in 50 % of all positive lymph invasion patients. Besides, FGF-10 gene upregulation was observed in 50 % of all tumors with a size larger than 5 cm (P value < 0.05) and 69 % of all tumors located in the colon (P value < 0.05). To our knowledge, this is the first time that FGF-10 expression is reported based on pathological features of colorectal cancer.

Cytokine fibroblast growth factor 10 (FGF10) polymorphisms are associated with risk of myopia in young children.

Myopia has become a major public health issue worldwide. Identification of genetic loci related to myopia in young children may advance our knowledge of the pathogenesis of myopia. Fibroblast growth factor 10 (FGF10) plays essential roles for the development of myopia through modulating extracellular matrix-associated genes. Studies revealed that genetic variants of FGF10 were associated with extreme myopia in adults. However, their associations with susceptibility of myopia in young children, which are less affected by confounding factors and more suitable for studying genetic factors of myopia, have not been explored. In the current study, we evaluated 13 tagSNPs that captured 100% of genetic variation in the FGF10 gene region for their associations with myopia in a large Chinese case-control study with 900 myopia children and 900 nonmyopia children. We found rs2973644 was significantly associated with increased risk of myopia (odds ratio [OR]: 1.26; 95% confidence intervals [CI]: 1.06-1.49; P = 0.009). furthermore, rs339501 (OR: 1.73; 95% CI: 1.18-2.53; P = 0.005), rs2973644 (OR: 1.57; 95% CI: 1.13-2.19; P = 0.007), and rs79002828 (OR: 1.83; 95% CI: 1.20-2.77; P = 0.005) were significantly associated with increased risk of high myopia in young children. Functional assessment of rs2973644 by luciferase assays revealed the risk G allele causes a higher expression level of FGF10 than the protective A allele. Our results do support that genetic variants of cytokine FGF10 are associated with susceptibility of myopia (as well as high myopia) in young children and further exploration are needed for myopia in children.

A functional variant alters binding of activating protein 1 regulating expression of FGF7 gene associated with chronic obstructive pulmonary disease

BackgroundGenome-wide association studies (GWASs) of a large cohort of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified multiple risk genes, including fibroblast growth factor 7 (FGF7). However, the underlying molecular mechanism influencing function of FGF7 and risk of COPD remains further study.MethodsIn this study, we replicated the genetic association of variants near the FGF7 gene in 258 Chinese Han patients with COPD and 311 healthy controls. Additionally, we functionally evaluated a candidate causal variant upstream of the FGF7 gene.ResultsThe most significant association was observed at rs12905203 (P = 5.9 × 10− 3, odd ratio, OR = 1.516) that explains associations of previously reported variants at the FGF7 locus. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays showed that the risk allele of the variant was bound to activator protein 1 transcription factors (c-Fos and c-Jun) with a significantly reduced affinity and associated with decreased mRNA expression of FGF7 in fibroblast cells at both resting and PMA/Ionomycin-stimulated conditions. Overexpression of c-Fos and c-Jun proteins or stimulation with PMA/Ionomycin significantly increases mRNA expression of FGF7 in fibroblast cells. Bioinformatic analysis showed that the variant overlaps with multiple genetic regulatory marks, suggesting the regulatory DNA element might function as an enhancer for the FGF7 gene. Luciferase enhancer activity assays demonstrated that the DNA sequences carrying the variant produce enhancer activity while the risk allele of the variant reduces its activity.ConclusionsIn this study, we demonstrated a consistent association of the FGF7 gene with COPD and mechanistically characterized a candidate functional variant upstream of the FGF7 gene. These data highlighted the important role of the risk variant and the FGF7 gene in influencing risk for COPD.

PWE-001 Field Cancerisation Theory In Colorectal Cancer (crc): What Role Do Fibroblast Growth Factors Have?

IntroductionCharacterisation of the molecular field defect around colorectal cancer (CRC) could enable identification of novel biomarkers that could be used for early detection of CRC. Previous studies have suggested fibroblast...

Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling

Fibroblast growth factor 10 (FGF10) is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation. In this study, we investigated the role of FGF10 as a lead induction factor for stem cell differentiation toward urothelial cell. To this end, human multipotent stem cell in vitro system was employed. Human amniotic fluid stem cells were co-cultured with immortalized bladder cancer lines to induce directed differentiation into urothelial cells. Urothelial markers, uroplakin II, III, and cytokeratin 8, were monitored by RT-PCR, immunocytochemistry, and Western blot analysis. Co-cultured stem cells began to express uroplakin II, III, and cytokeratin 8. Targeted FGF10 gene knockdown from bladder cancer cells abolished the directed differentiation. In addition, when FGF10 downstream signaling was blocked with the Mek inhibitor, the co-culture system lost the capacity to induce urothelial differentiation. Exogenous addition of recombinant FGF10 protein promoted stem cell differentiation into urothelium cell lineage. Together, this report suggests that paracrine FGF10 signaling stimulates the differentiation of human stem cell into urothelial cells. Current study provides insight into the potential role of FGF10 as a lead growth factor for bladder regeneration and its therapeutic application for bladder transplantation.

Pulmonary FGF9 Gene Expression is Downregulated during the Pseudoglandular Stage in Nitrofen-Induced Hypoplastic Lungs

The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains unclear. Fibroblast growth factor 9 (FGF9) is an essential component of the gene network that regulates lung development. FGF9 knockouts exhibit disrupted mesenchymal proliferation and reduced airway branching. The authors hypothesized that pulmonary FGF9 gene expression is downregulated during the pseudoglandular stage in nitrofen-induced hypoplastic lungs. Pregnant rats received either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were dissected on D15 and D18, and were divided into controls, hypoplastic lungs with CDH (CDH+) and hypoplastic lungs without CDH (CDH-). Pulmonary FGF9 gene expression levels were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to investigate FGF9 protein expression/distribution. Relative messenger RNA levels of FGF9 were significantly decreased on D15 in hypoplastic lungs compared with controls (p < 0.01), and on D18 in CDH+ and CDH- compared with controls (p< 0.05, respectively). Immunoreactivity of FGF9 was markedly diminished in mesothelium and distal airway epithelium on D15 and decreased in overall intensity on D18 in hypoplastic lungs compared with controls. Downregulation of FGF9 gene expression during the pseudoglandular stage may cause pulmonary hypoplasia in the nitrofen model by decreasing distal airway epithelial and mesenchymal proliferation throughout the branching morphogenesis.

A Functional Polymorphism at the FGF10 Gene Is Associated With Extreme Myopia

Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. The expression levels of FGF10 gene were compared among the form deprivation myopic (FDM) eyes, the fellow eyes of the FDM group, and the healthy eyes of experimental mice. In the present study 1020 cases (≤-6.0 diopters [D]) and 960 controls (≥-1.5 D) were enrolled from a Chinese population. Eight tagging SNPs were genotyped to test for an association between genotypes and myopia. The luciferase reporter assay was conducted for the particular SNP to assess the allelic effect on gene expression. The sclera of FDM eyes had a 2.57-fold higher level of FGF10 mRNA (P = 0.018) than the fellow eyes. Although no SNP was associated with high myopia, SNP rs339501 was significantly associated with extreme myopia (≤-10 D, P = 0.008) and the odds ratio (OR) was 1.58 for G allele carriers. The luciferase assay showed that the risk G allele significantly caused a higher expression level than the A allele (P = 0.011). The evidence suggested FGF10 to be a risk factor for myopia. The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. It is concluded that the FGF10 could have been involved in the development of myopia.