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繊維芽細胞増殖因子の発現を介した血小板由来増殖因子による唾液腺形態形成の制御

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繊維芽細胞増殖因子の発現を介した血小板由来増殖因子による唾液腺形態形成の制御

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山本, 晋也
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鹿児島大学
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2009-2010年度科学研究費補助金(若手研究(B))研究成果報告書 課題番号:21792089 研究代表者:山本晋也 (鹿児島大学医学部・歯学部附属病院助教)マウス顎下腺の器官培養において、PDGF-AAあるいはPDGF-BBを添加すると、その受容体は間葉に存在しているのにも関わらず、唾液腺組織...

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Material Type
文書・図像類
Author/Editor
山本, 晋也
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Alternative Title
Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression
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jpn
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一般
Note (General)
2009-2010年度科学研究費補助金(若手研究(B))研究成果報告書 課題番号:21792089 研究代表者:山本晋也 (鹿児島大学医学部・歯学部附属病院助教)
マウス顎下腺の器官培養において、PDGF-AAあるいはPDGF-BBを添加すると、その受容体は間葉に存在しているのにも関わらず、唾液腺組織の上皮細胞増殖が亢進し、分岐形態形成が促進され、PDGF-A及びB siRNAを用いてPDGF mRNA発現の抑制を行なった場合、上皮組織での細胞増殖が抑えられ分岐形態形成が減少した。一方、PDGF-AAはFGF3とFGF7の発現を誘導し、PDGF-BB はFGF1、FGF3、FGF7及びFGF10の発現を誘導した。しかしPDGF-A及びB siRNAはFGF3、FGF7、FGF10の発現を抑制した。この結果は、PDGFが顎下腺間葉におけるFGFの発現を制御していることを示唆している。
A coordinated reciprocal interaction between epithelium and mesenchyme is involved in salivary gland morphogenesis. The submandibular glands (SMGs) of Wnt1-Cre/R26R mice have been shown positive for mesenchyme, whereas the epithelium is beta-galactosidase-negative, indicating that most mesenchymal cells are derived from cranial neural crest cells. Platelet-derived growth factor (PDGF) receptor alpha is one of the markers of neural crest-derived cells. In this study, we analyzed the roles of PDGFs and their receptors in the morphogenesis of mouse SMGs. PDGF-A was shown to be expressed in SMG epithelium, whereas PDGF-B, PDGFRalpha, and PDGFRbeta were expressed in mesenchyme. Exogenous PDGF-AA and -BB in SMG organ cultures demonstrated increased levels of branching and epithelial proliferation, although their receptors were found to be expressed in mesenchyme. In contrast, short interfering RNA for Pdgfa and -b as well as neutralizing antibodies for PDGF-AB and -BB showed decreased branching. PDGF-AA induced the expression of the fibroblast growth factor genes Fgf3 and -7, and PDGF-BB induced the expression of Fgf1, -3, -7, and -10, whereas short interfering RNA for Pdgfa and Pdgfb inhibited the expression of Fgf3, -7, and -10, indicating that PDGFs regulate Fgf gene expression in SMG mesenchyme. The PDGF receptor inhibitor AG-17 inhibited PDGF-induced branching, whereas exogenous FGF7 and -10 fully recovered. Together, these results indicate that fibroblast growth factors function downstream of PDGF signaling, which regulates Fgf expression in neural crest-derived mesenchymal cells and SMG branching morphogenesis. Thus, PDGF signaling is a possible mechanism involved in the interaction between epithelial and neural crest-derived mesenchyme.