癌における血管新生に関与している (同：VEGF。対：angiostatin, endostatin, vasculostatin)
細胞間マトリックスに蓄えらているbFGFはプロテアーゼによって放出される (BPT.201)
mitogenである：mesenchymall, neural, and epithelial organ

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/03 16:10:34」(JST)

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Basic fibroblast growth factor, also known as bFGF, FGF2 or FGF-β,^[1] is a member of the fibroblast growth factor family.^[2]

Function [edit]

In normal tissue, basic fibroblast growth factor is present in basement membranes and in the subendothelial extracellular matrix of blood vessels. It stays membrane-bound as long as there is no signal peptide.

It has been hypothesized that, during both wound healing of normal tissues and tumor development, the action of heparan sulfate-degrading enzymes activates bFGF, thus mediating the formation of new blood vessels, a process known as angiogenesis.

In addition, it is synthesized and secreted by human adipocytes and the concentration of bFGF correlates with the BMI in blood samples. In this study, bFGF was also shown to act on preosteoblasts - in the form of an increased proliferation^{[disambiguation needed]} - after binding to fibroblast growth factor receptor 1 and activating phosphoinositide 3-kinase.^[3]

bFGF has been shown in preliminary animal studies to protect the heart from injury associated with a heart attack, reducing tissue death and promoting improved function after reperfusion.^[4]

Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety. [3]

Additionally, bFGF is a critical component of human embryonic stem cell culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce gremlin expression which in turn is known to inhibit the induction of differentiation by bone morphogenetic proteins.^[5] It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems.^[6] FGF2, in conjunction with BMP4, promote differentiation of stem cells to mesodermal lineages. After differentiation, BMP4 and FGF2 treated cells generally produces higher amounts of osteogenic and chondorgenic differentiation than untreated stem cells.^[7]

Interactions [edit]

Basic fibroblast growth factor has been shown to interact with casein kinase 2, alpha 1,^[8] RPL6^[9] and ribosomal protein S19.^[10]

References [edit]

^ Horst Ibelgaufts' COPE: FGF-beta
^ Kim HS (1998). "Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping". Cytogenet. Cell Genet. 83 (1-2): 73. doi:10.1159/000015129. PMID 9925931.
^ Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S. (2012). "Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation.". Mol Cell Endocrinol. 349 (2): 180–188. doi:10.1016/j.mce.2011.10.018. PMID 22040599.
^ House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J. (2003). "Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia.". Circulation 108 (1): 3140–3148. doi:10.1161/01.CIR.0000105723.91637.1C. PMID 14656920.
^ Pereira RC, Economides AN, Canalis E (December 2000). "Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts". Endocrinology 141 (12): 4558–63. doi:10.1210/en.141.12.4558. PMID 11108268.
^ Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H (2006). "A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells". Biochem Biophys Res Commun 346 (1): 131–9. doi:10.1016/j.bbrc.2006.05.086. PMID 16753134.
^ Lee, T. J.; Jang, J.; Kang, S.; Jin, M.; Shin, H.; Kim, D. W.; Kim, B. S. (2013). "Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment". Biochemical and Biophysical Research Communications 430 (2): 793–797. doi:10.1016/j.bbrc.2012.11.067. PMID 23206696. edit
^ Skjerpen, Camilla Skiple; Nilsen Trine, Wesche Jørgen, Olsnes Sjur (August 2002). "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". EMBO J. (England) 21 (15): 4058–69. doi:10.1093/emboj/cdf402. ISSN 0261-4189. PMC 126148. PMID 12145206.
^ Shen, B; Arese M, Gualandris A, Rifkin D B (November 1998). "Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107". Biochem. Biophys. Res. Commun. (UNITED STATES) 252 (2): 524–8. doi:10.1006/bbrc.1998.9677. ISSN 0006-291X. PMID 9826564.
^ Soulet, F; Al Saati T, Roga S, Amalric F, Bouche G (November 2001). "Fibroblast growth factor-2 interacts with free ribosomal protein S19". Biochem. Biophys. Res. Commun. (United States) 289 (2): 591–6. doi:10.1006/bbrc.2001.5960. ISSN 0006-291X. PMID 11716516.

External links [edit]

Basic Fibroblast Growth Factor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on chromosome 4 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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1. 難治性狭心症マネージメントのための血管新生療法 therapeutic angiogenesis for management of refractory angina
2. 原発性骨髄線維症における病態 pathogenetic mechanisms in primary myelofibrosis
3. 全身性硬化症（強皮症）の病因 pathogenesis of systemic sclerosis scleroderma
4. 糖尿病性網膜症：病因 diabetic retinopathy pathogenesis
5. 悪性神経膠腫の病因と分子生物学 pathology and molecular pathogenesis of diffuse gliomas

English Journal

Neurogenesis of Neural Crest-Derived Periodontal Ligament Stem Cells by EGF and bFGF.

Fortino VR, Chen RS, Pelaez D, Cheung HS.Author information Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, Florida.AbstractNeuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells, the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor, and basic fibroblast growth factor. Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy. A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein, demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole-cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na(+) ) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine. J. Cell. Physiol. 229: 479-488, 2014. © 2013 Wiley Periodicals, Inc.
Journal of cellular physiology.J Cell Physiol.2014 Apr;229(4):479-88. doi: 10.1002/jcp.24468.
Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem ce
PMID 24105823

Bone marrow-derived myofibroblasts promote colon tumorigenesis through the IL-6/JAK2/STAT3 pathway.

Zhu L1, Cheng X2, Ding Y2, Shi J3, Jin H3, Wang H3, Wu Y2, Ye J4, Lu Y4, Wang TC5, Yang CS3, Tu SP6.Author information 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.2Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.3Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.4Emergency Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.5Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.6Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: tushuiping@yahoo.com.AbstractBone marrow-derived myofibroblasts (BMFs) have been shown to promote tumor growth. Here, we found that BMFs or BMF conditioned medium (BMF-CM) induced cancer stem cell-like sphere formation of colon cancer cells. The co-cultured BMFs, but not co-cultured cancer cells, expressed higher levels of IL-6 than BMFs or cancer cells cultured alone. Anti-mouse IL-6 neutralizing antibody, JAK2 inhibitors and STAT3 knockdown in mouse cancer cells reduced BMF- and BMF-CM-induced sphere formation of colon cancer cells. When co-injected, BMFs significantly enhanced tumorigenesis of colon cancer cells in mice. Our results demonstrate that BMFs promote tumorigenesis via the activation of the IL-6/JAK2/STAT3 pathway.
Cancer letters.Cancer Lett.2014 Feb 1;343(1):80-9. doi: 10.1016/j.canlet.2013.09.017. Epub 2013 Oct 18.
Bone marrow-derived myofibroblasts (BMFs) have been shown to promote tumor growth. Here, we found that BMFs or BMF conditioned medium (BMF-CM) induced cancer stem cell-like sphere formation of colon cancer cells. The co-cultured BMFs, but not co-cultured cancer cells, expressed higher levels of IL-6
PMID 24145153

Regulation of human mesenchymal stem cells differentiation into chondrocytes in extracellular matrix-based hydrogel scaffolds.

Du M1, Liang H1, Mou C1, Li X1, Sun J1, Zhuang Y1, Xiao Z2, Chen B2, Dai J3.Author information 1Division of Nanobiomedicine Research and Suzhou Key Laboratory of Nanobiomedical Characterization, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), 398 Ruoshui Road, Suzhou Dushu Lake Science and Education Innovation District (SEID), Suzhou Industrial Park (SIP), Suzhou 215123, PR China.2State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), Beijing 100190, PR China.3Division of Nanobiomedicine Research and Suzhou Key Laboratory of Nanobiomedical Characterization, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences (CAS), 398 Ruoshui Road, Suzhou Dushu Lake Science and Education Innovation District (SEID), Suzhou Industrial Park (SIP), Suzhou 215123, PR China; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), Beijing 100190, PR China. Electronic address: jwdai@genetics.ac.cn.AbstractTo induce human mesenchymal stem cells (hMSCs) to differentiate into chondrocytes in three-dimensional (3D) microenvironments, we developed porous hydrogel scaffolds using the cartilage extracellular matrix (ECM) components of chondroitin sulfate (CS) and collagen (COL). The turbidity and viscosity experiments indicated hydrogel could form through pH-triggered co-precipitation when pH=2-3. Enzyme-linked immunosorbent assay (ELISA) confirmed the hydrogel scaffolds could controllably release growth factors as envisaged. Transforming growth factor-β (TGF-β) was released to stimulate hMSCs differentiation into chondrocytes; and then collagen binding domain-basic fibroblast growth factor (CBD-bFGF) was released to improve the differentiation and preserve the chondrocyte phenotype. In in vitro cell culture experiments, the differentiation processes were compared in different microenvironments: 2D culture in culture plate as control, 3D culture in the fabricated scaffolds without growth factors (CC), the samples with CBD-bFGF (CC-C), the samples with TGF-β (CC-T), the samples with CBD-bFGF/TGF-β (CC-CT). Real-time polymerase chain reaction (RT-PCR) revealed the hMSC marker genes of CD44 and CD105 decreased; at the same time the chondrocyte marker genes of collagen type II and aggrecan increased, especially in the CC-CT sample. Immunostaining results further confirmed the hMSC marker protein of CD 44 disappeared and the chondrocyte marker protein of collagen type II emerged over time in the CC-CT sample. These results imply the ECM-based hydrogel scaffolds with growth factors can supply suitable 3D cell niches for hMSCs differentiation into chondrocytes and the differentiation process can be regulated by the controllably released growth factors.
Colloids and surfaces. B, Biointerfaces.Colloids Surf B Biointerfaces.2014 Feb 1;114:316-23. doi: 10.1016/j.colsurfb.2013.10.001. Epub 2013 Oct 24.
To induce human mesenchymal stem cells (hMSCs) to differentiate into chondrocytes in three-dimensional (3D) microenvironments, we developed porous hydrogel scaffolds using the cartilage extracellular matrix (ECM) components of chondroitin sulfate (CS) and collagen (COL). The turbidity and viscosity
PMID 24231133

Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi‑1 leukemia cells.

Zhang ZH1, Hao CL1, Liu P2, Tian X3, Wang LH1, Zhao L1, Zhu CM1.Author information 1Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, P.R. China.2The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei 050000, P.R. China.3Chinese PLA 89 Hospital, Weifang, Shandong 261000, P.R. China.AbstractHistone deacetylase (HDAC) inhibitors have been reported to inhibit tumor angiogenesis via the downregulation of angiogenic factors. Our previous in vitro studies demonstrated that valproic acid (VPA) exerted antitumor effects on Kasumi‑1 cells, which are human acute myeloid leukemia cells with an 8;21 chromosome translocation. In the present study, the effects of VPA on tumor angiogenesis were investigated in mice transplanted with Kasumi‑1 cells. Semi‑quantitative reverse transcription‑polymerase chain reaction, western blotting and immunohistochemistry were used to detect the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR2) and basic fibroblast growth factor (bFGF). The tumor microvessel density was measured following staining with an anti‑CD34 antibody. Chromatin immunoprecipitation was used to study the effect of VPA‑induced histone hyperacetylation on VEGF transcription. An intraperitoneal injection of VPA inhibited tumor growth and angiogenesis in mice transplanted with Kasumi‑1 cells. The mRNA and protein expression of VEGF, VEGFR2 and bFGF were inhibited by VPA treatment. In addition, VPA downregulated HDAC, increased histone H3 acetylation and enhanced the accumulation of hyperacetylated histone H3 on the VEGF promoters. The findings of the present study indicate that VPA, an HDAC inhibitor, exerts an antileukemic effect through an anti‑angiogenesis mechanism. In conclusion, the mechanism underlying VPA‑induced anti‑angiogenesis is associated with the suppression of angiogenic factors and their receptors. VPA may increase the accumulation of acetylated histones on the VEGF promoters, which possibly contributes to the regulation of angiogenic factors.
Molecular medicine reports.Mol Med Rep.2014 Feb;9(2):443-9. doi: 10.3892/mmr.2013.1834. Epub 2013 Nov 28.
Histone deacetylase (HDAC) inhibitors have been reported to inhibit tumor angiogenesis via the downregulation of angiogenic factors. Our previous in vitro studies demonstrated that valproic acid (VPA) exerted antitumor effects on Kasumi‑1 cells, which are human acute myeloid leukemia cells with a
PMID 24297248

Japanese Journal

bFGF徐放性材料を用いた骨再生モデルにおける骨再生と血管新生の検討(岩手医科大学学位審査報告)

大橋祐生
岩手医科大学歯学雑誌 36(2), 124-125, 2011-08-19
NAID 110008733448

P-68 水酸化ナトリウム水溶液を用いたラット食道狭窄モデルにおけるbFGFの治療効果(研究・その他2,ポスターセッション,第48回日本小児外科学会学術集会)

大片祐一,久松千恵子,西島栄治
日本小児外科学会雑誌 47(4), 621, 2011-07-05
NAID 110008735190

bFGF徐放性材料を用いた骨再生モデルにおける骨再生と血管新生の検討

大橋祐生,藤村朗
岩手医科大学歯学雑誌 36(1), 19-34, 2011-05-10
… 防御の面において重要であると考えられる.本研究は,bFGF徐放システムによる骨再生モデルを用いて,マイクロフォーカスCTにより同一個体の経時的な骨再生の経過を観察し,連続組織標本を作製することで,骨再生と血管新生の関係を明らかにすることを目的とした.実験方法は,10週齢のWistar系ラットの頭頂骨に直径7mmの骨欠損を形成し,実験群にはbFGF 10μg含有酸性ゼラチンディスクを埋入した.また,対照 …
NAID 110008752157

Related Pictures

★リンクテーブル★

リンク元	「成長因子」「endostatin」「線維芽細胞増殖因子」「血管新生」「塩基性線維芽細胞成長因子」

「成長因子」

Fibroblast growth factor 2 (basic)
	; PDB rendering based on 1bas.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1BAS, 1BFB, 1BFC, 1BFF, 1BFG, 1BLA, 1BLD, 1CVS, 1EV2, 1FGA, 1FQ9, 1II4, 1IIL, 2BFH, 2FGF, 4FGF
Identifiers
Symbols	FGF2; BFGF; FGF-2; FGFB; HBGF-2
External IDs	OMIM: 134920 MGI: 95516 HomoloGene: 1521 ChEMBL: 3107 GeneCards: FGF2 Gene
Gene Ontology
Molecular function	• fibroblast growth factor receptor binding; • cytokine activity; • protein binding; • growth factor activity; • heparin binding; • fibroblast growth factor binding; • ligand-dependent nuclear receptor transcription coactivator activity; • chemoattractant activity;
Cellular component	• extracellular region; • extracellular space; • nucleus; • cytosol;
Biological process	• activation of MAPKK activity; • activation of MAPK activity; • MAPK import into nucleus; • branching involved in ureteric bud morphogenesis; • organ induction; • positive regulation of endothelial cell proliferation; • cell migration involved in sprouting angiogenesis; • phosphatidylinositol biosynthetic process; • C21-steroid hormone biosynthetic process; • apoptotic process; • chemotaxis; • signal transduction; • epidermal growth factor receptor signaling pathway; • Ras protein signal transduction; • nervous system development; • positive regulation of cell proliferation; • negative regulation of cell proliferation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • organ morphogenesis; • glial cell differentiation; • negative regulation of fibroblast migration; • positive regulation of phospholipase C activity; • substantia nigra development; • positive regulation of cerebellar granule cell precursor proliferation; • hyaluronan catabolic process; • negative regulation of cell growth; • lung development; • inositol phosphate biosynthetic process; • wound healing; • positive regulation of cell fate specification; • positive regulation of blood vessel endothelial cell migration; • negative regulation of blood vessel endothelial cell migration; • positive regulation of phosphatidylinositol 3-kinase activity; • innate immune response; • positive regulation of osteoblast differentiation; • regulation of angiogenesis; • positive regulation of angiogenesis; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • regulation of retinal cell programmed cell death; • neurotrophin TRK receptor signaling pathway; • phosphatidylinositol-mediated signaling; • embryonic morphogenesis; • response to axon injury; • stem cell development; • positive chemotaxis; • release of sequestered calcium ion into cytosol; • regulation of cell cycle; • positive regulation of cell division; • positive regulation of cardiac muscle cell proliferation; • corticotropin hormone secreting cell differentiation; • thyroid-stimulating hormone-secreting cell differentiation; • negative regulation of cell death; • chondroblast differentiation; • mammary gland epithelial cell differentiation; • negative regulation of wound healing; • positive regulation of ERK1 and ERK2 cascade;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: 成長因子 growth factor
同: 成長促進因子 growth-promoting substance、発育因子、増殖因子

[show details]

発育因子 : 約 8,070 件
成長因子 : 約 675,000 件
増殖因子 : 約 1,290,000 件

発育因子 growth : 約 12,100 件
成長因子 growth : 約 319,000 件
増殖因子 growth : 約 157,000 件

TGF-β
PDGF

血管新生

angiogenic factor

VEGF
bFGF

angiostasis

「endostatin」

　　[★]

関: 血管新生、コラーゲン

XVIII型コラーゲンの分解産物
angiostatic factor(anti-angiogenesis)

angiogenic factors such as VEGF and bFGF have relatively long half-lives in the blood compared with angiostatic factos such as endostain or angiostatin.

large tumors often produce sufficient amounts of angiostatic factors to suppress the growth of blood vessels in small, undetectable tumors present elsewhere in the body.