國家衛生研究院 NHRI:Item 3990099045/1489
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    題名: Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-beta 1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells
    其他題名: Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-β1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells
    作者: Lien, SC;Usami, S;Chien, S;Chiu, JJ
    貢獻者: Division of Medical Engineering Research
    摘要: Transforming growth factor-beta 1 (TGF-beta 1) is known to induce phenotypic modulation of mesenchymal cells to SMCs. However, the intracellular signals regulating induction of the SMC phenotype of mesenchymal cells have not been fully clarified. In the present study, we examined the role of the mitogen-activated protein kinase (MAPK) superfamily and phosphatidylinositol. 3-kinase (P13K)/Akt in the TGF-beta 1 mediated phenotypic modulation of 10T1/2 mesenchymal cells to SMCs characterized by the expression of SMC-specific markers, including smooth muscle alpha-actin (SM alpha-actin), myosin heavy chain(SM-NMC),and protein 22-alpha(SM22 alpha). The results showed the following: (1) TGF-beta 1 induced SM alpha-actin and SM-MHC expressions in 10T1/2 cells in a time-dependent manner. (2) TGF-beta 1 induced biphasic increases in extracellular signal-regulated kinase (ERK), p38 MAPK, c-Jun-NH2-terminal kinase (JNK), and Akt phosphorylation. (3) The inhibitor for P13K/Akt (i.e., LY294002), but not those for MAPKs (i.e.,S13203580,PLD98059, and SP600125), attenuated the TGF-beta 1-induced SM alpha-actin and SM-NMC expressions in 10T1/2 cells; in addition, transfection of 10T1/2 cells with the Akt-specific small interfering RNA (siRNA) significantly reduced their SM alpha-actin and SM-MHC expressions. (4) LY294002 and the Akt-specific siRNA inhibited the TGF-beta 1-induced SM22 alpha gene expression and promoter activity, suggesting that the TGF-beta 1-induced gene expression was mediated by P13K/Akt at the transcriptional level. (5) LY294002 inhibited the TGF-beta 1-induced gene expression and DNA binding activity of serum response factor (SRF). These results indicate that TGF-beta 1 is capable of inducing the SMC phenotype of 10T1/2 cells and that this induction is mediated through the P13K/Akt signaling pathway. (c) 2005 Elsevier Inc. All rights reserved.
    關鍵詞: Cell Biology
    日期: 2006-08
    關聯: Cellular Signalling. 2006 Aug;18(8):1270-1278.
    Link to: http://dx.doi.org/10.1016/j.cellsig.2005.10.013
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0898-6568&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000238002700019
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33646381642
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