• Development and Reproduction
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• v.17 no.4
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• pp.389-397
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• 2013

FGF9/16/20 signaling pathway specify the developmental fates of notochord, mesenchyme, and neural cells in ascidian embryos. Although a conserved Ras/MEK/Erk/Ets pathway is known to be involved in this signaling, the detailed mechanisms of regulation of FGF signaling pathway have remained largely elusive. In this study, we have isolated Hr-Erf, an ascidian orthologue of vertebrate Erf, to elucidate interactions of transcription factors involved in FGF signaling of the ascidian embryo. The Hr-Erf cDNA encompassed 3110 nucleotides including sequence encoded a predicted polypeptide of 760 amino acids. The polypeptide had the Ets DNA-binding domain in its N-terminal region. In adult animals, Hr-Erf mRNA was predominantly detected in muscle, and at lower levels in ganglion, gills, gonad, hepatopancreas, and stomach by quantitative real-time PCR (QPCR) method. During embryogenesis, Hr-Erf mRNA was detected from eggs to early developmental stage embryos, whereas the transcript levels were decreased after neurula stage. Similar to the QPCR results, maternal transcripts of Hr-Erf was detected in the fertilized eggs by whole-mount in situ hybridization. Maternal mRNA of Hr-Erf was gradually lost from the neurula stage. Zygotic expression of Hr-Erf started in most blastomeres at the 8-cell stage. At gastrula stage, Hr-Erf was specifically expressed in the precursor cells of brain and mesenchyme. When MEK inhibitor was treated, embryos resulted in loss of Hr-Erf expression in mesenchyme cells, and in excess of Hr-Erf in a-line neural cells. These results suggest that zygotic Hr-Erf products are involved in specification of mesenchyme and neural cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.2
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• pp.103-115
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• 2009

In vertebrates, the face is mainly formed with neural crest derived neural crest cells by the inherent programs and the interactive environmental factors. Extracellular signaling-regulated kinase (Erk) is one of such programs to regulate the various cellular functions. And retinoic acid (RA) also plays an important role as a regulator in differentiation process at various stages of vertebrate embryogenesis. We wanted to know that the segregation as well as the patterning of maxillary and mandibular structure is greatly influenced by the maxillomandibular cleft (MMC) and the failure of this development may result in the maxillomandibular fusion (syngnathia) or other patterning related disorder. It has been well documented that the epithelium at this cleft region has significant expression of Fibroblast growth factor (Fgf) 8, and it is essential for the patterning of the first arch derived structures. By the morphological, skeletal, cell proliferation and apoptotic, and hybridization analysis, we checked the effects of Erk inhibition and/or RA activation onto MMC and could observe that Erk and RA signaling is individually and synergically involved in the facial patterning in terms of FGF signaling pathway via Barx-l. So RA and Erk signaling work together for the MMC patterning and the segregation of maxilla-mandible by controlling the Fgf-related signaling pathways. And the abnormality in MMC brought by aberrant Fgf signaling may result in the disturbances of maxillary-mandibular segregation.

• Journal of Life Science
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• v.26 no.3
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• pp.331-337
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• 2016

Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.

• Proceedings of the Zoological Society Korea Conference
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• 2001.04a
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• pp.70.2-70
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• 2001

No Abstract, See Full Text

• Journal of Life Science
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• v.34 no.4
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• pp.227-235
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• 2024

Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

• Animal Bioscience
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• v.37 no.5
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• pp.929-943
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• 2024

Objective: The present study was executed to explore the molecular mechanism of fibroblast growth factor 10 (FGF10) gene in bovine adipogenesis. Methods: 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. Results: 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 down-regulation (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. Conclusion: 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.

• Development and Reproduction
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• v.6 no.2
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• pp.77-82
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• 2002

In ascidians, a primitive chordate, maternal cytoplasmic factors and inductive interactions are involved in the specification of cell fates in early embryos. The larval structure of ascidians is relatively simple, and the major mesodermal tissues of the tadpole larva are notochord, muscle, and mesenchyme. Formation of muscle cells is a cell-autonomous process, and localized maternal macho-l mRNA specify muscle fate in the posterior marginal zone of the early embryo. In contrast, inductive influence from endoderm precursors plays important roles in the specification of notochord and mesenchyme fates. FGF-Ras-MAPK signaling is involved In the induction of both tissues. The difference in responsiveness of the posterior mesenchyme and anterior notochord precursors to FGF signaling is caused by the presence or absence of intrinsic factors that inherited from the posterior-vegetal egg cytoplasm, respectively. In these inductions, directed signal polarizes the induced cells and promotes asymmetric cell divisions to produce two daughter cells with distinct fates.

• Animal Bioscience
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• v.36 no.4
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• pp.570-583
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• 2023

Objective: Fibroblast growth factors (FGFs) play critical roles in embryo development, and immune responses to infectious diseases. In this study, to investigate the roles of FGFs, we performed genome-wide identification, expression, and functional analyses of FGF family members in chickens. Methods: Chicken FGFs genes were identified and analyzed by using bioinformatics approach. Expression profiles and Hierarchical cluster analysis of the FGFs genes in different chicken tissues were obtained from the genome-wide RNA-seq. Results: A total of 20 FGF genes were identified in the chicken genome, which were classified into seven distinct groups (A-F) in the phylogenetic tree. Gene structure analysis revealed that members of the same clade had the same or similar exon-intron structure. Chromosome mapping suggested that FGF genes were widely dispersed across the chicken genome and were located on chromosomes 1, 4-6, 9-10, 13, 15, 28, and Z. In addition, the interactions among FGF proteins and between FGFs and mitogen-activated protein kinase (MAPK) proteins are limited, indicating that the remaining functions of FGF proteins should be further investigated in chickens. Kyoto encyclopedia of genes and genomes pathway analysis showed that FGF gene interacts with MAPK genes and are involved in stimulating signaling pathway and regulating immune responses. Furthermore, this study identified 15 differentially expressed genes (DEG) in 21 different growth stages during early chicken embryo development. RNA-sequencing data identified the DEG of FGFs on 1- and 3-days post infection in two indigenous Ri chicken lines infected with the highly pathogenic avian influenza virus H5N1 (HPAIV). Finally, all the genes examined through quantitative real-time polymerase chain reaction and RNA-Seq analyses showed similar responses to HPAIV infection in indigenous Ri chicken lines (R² = 0.92-0.95, p<0.01). Conclusion: This study provides significant insights into the potential functions of FGFs in chickens, including the regulation of MAPK signaling pathways and the immune response of chickens to HPAIV infections.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.323-328
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• 2017

Angiogenesis is a process including members of the angiogenic factors. In particular, fibroblast growth factor 2 (FGF2) is considered the most potent angiogenic factor because it promotes cell proliferation and tube formation. A recent study reported that fucoidan derived from marine plant potentiated FGF-2 induced tube formation in human endothelial cells. On the other hand, the molecular mechanisms involved in the angiogenic activity of fucoidan and FGF2 are unknown. In this study, a fucoidan treatment promoted angiogenesis induced by FGF2. The effects of fucoidan on FGF2-induced angiogenesis were confirmed by a proliferation assay using a CellTiter96 Aqueous One solution after a treatment with fucoidan and FGF2. The tube formation and wound healing assay for the angiogenic activity were also confirmed. Reverse transcription PCR showed a change in the mRNA of vascular endothelial growth factor-A (VEGF-A), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase9 (MMP9), and the signal transducer and activator of transcription3 (STAT3). In summary, the Fucoidan/FGF2 treatment induced an increase in cell proliferation, improved the tube formation and wound healing activity, and altered the STAT3, VEGF-A, ICAM-1, and MMP9 mRNA expression levels. Further research will be needed to provide a scientific explanation in terms of cell-signaling and confirm the present findings.

• Molecules and Cells
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• v.41 no.2
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• pp.110-118
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• 2018

The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 ($0.6{\mu}M$) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course in vivo. Resultant cells showed upregulated expression levels of FGF8 and WNT1. The addition of exogenous FGF8 further increased WNT1 expression by 2.6 fold. Gene ontology following microarray analysis confirmed that IsO-like cells enriched the expression of MHB-related genes by 40 fold compared to control cells. Lysates and conditioned media of IsO-like cells contained functional FGF8 and WNT1 proteins that could induce MHB-related genes in differentiating ESCs. The method for generating functional IsO-like cells described in this study could be used to study human central nervous system development and congenital malformations of the midbrain and hindbrain.