TY - JOUR
T1 - Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-β1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells
AU - Lien, Sheng Chieh
AU - Usami, Shunichi
AU - Chien, Shu
AU - Chiu, Jeng Jiann
N1 - Funding Information:
This work was supported by grants ME-094-PP-06 (Jeng-Jiann Chiu) from the National Health Research Institutes, 94-3112-B-400-005 and 94-2321-B-400-002 from the National Science Council, Taiwan, ROC, and HL19454 (Shu Chien) from the National Heart, Lung, and Blood Institute, USA. The work was conducted in part in affiliation with the Center of Tissue Engineering and Stem Cell Research, National Chung-Hsing University, Taichung, Taiwan, ROC.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Transforming growth factor-β1 (TGF-β1) 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 (PI3K)/Akt in the TGF-β1-mediated phenotypic modulation of 10T1/2 mesenchymal cells to SMCs characterized by the expression of SMC-specific markers, including smooth muscle α-actin (SMα-actin), myosin heavy chain (SM-MHC), and protein 22-α (SM22α). The results showed the following: (1) TGF-β1 induced SMα-actin and SM-MHC expressions in 10T1/2 cells in a time-dependent manner. (2) TGF-β1 induced biphasic increases in extracellular signal-regulated kinase (ERK), p38 MAPK, c-Jun-NH2-terminal kinase (JNK), and Akt phosphorylation. (3) The inhibitor for PI3K/Akt (i.e., LY294002), but not those for MAPKs (i.e., SB203580, PD98059, and SP600125), attenuated the TGF-β1-induced SMα-actin and SM-MHC expressions in 10T1/2 cells; in addition, transfection of 10T1/2 cells with the Akt-specific small interfering RNA (siRNA) significantly reduced their SMα-actin and SM-MHC expressions. (4) LY294002 and the Akt-specific siRNA inhibited the TGF-β1-induced SM22α gene expression and promoter activity, suggesting that the TGF-β1-induced gene expression was mediated by PI3K/Akt at the transcriptional level. (5) LY294002 inhibited the TGF-β1-induced gene expression and DNA binding activity of serum response factor (SRF). These results indicate that TGF-β1 is capable of inducing the SMC phenotype of 10T1/2 cells and that this induction is mediated through the PI3K/Akt signaling pathway.
AB - Transforming growth factor-β1 (TGF-β1) 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 (PI3K)/Akt in the TGF-β1-mediated phenotypic modulation of 10T1/2 mesenchymal cells to SMCs characterized by the expression of SMC-specific markers, including smooth muscle α-actin (SMα-actin), myosin heavy chain (SM-MHC), and protein 22-α (SM22α). The results showed the following: (1) TGF-β1 induced SMα-actin and SM-MHC expressions in 10T1/2 cells in a time-dependent manner. (2) TGF-β1 induced biphasic increases in extracellular signal-regulated kinase (ERK), p38 MAPK, c-Jun-NH2-terminal kinase (JNK), and Akt phosphorylation. (3) The inhibitor for PI3K/Akt (i.e., LY294002), but not those for MAPKs (i.e., SB203580, PD98059, and SP600125), attenuated the TGF-β1-induced SMα-actin and SM-MHC expressions in 10T1/2 cells; in addition, transfection of 10T1/2 cells with the Akt-specific small interfering RNA (siRNA) significantly reduced their SMα-actin and SM-MHC expressions. (4) LY294002 and the Akt-specific siRNA inhibited the TGF-β1-induced SM22α gene expression and promoter activity, suggesting that the TGF-β1-induced gene expression was mediated by PI3K/Akt at the transcriptional level. (5) LY294002 inhibited the TGF-β1-induced gene expression and DNA binding activity of serum response factor (SRF). These results indicate that TGF-β1 is capable of inducing the SMC phenotype of 10T1/2 cells and that this induction is mediated through the PI3K/Akt signaling pathway.
KW - 10T1/2 mesenchymal cell
KW - Signal transduction
KW - Smooth muscle cell
KW - Transforming growth factor-β1
UR - http://www.scopus.com/inward/record.url?scp=33646381642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646381642&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2005.10.013
DO - 10.1016/j.cellsig.2005.10.013
M3 - Article
C2 - 16310342
AN - SCOPUS:33646381642
SN - 0898-6568
VL - 18
SP - 1270
EP - 1278
JO - Cellular Signalling
JF - Cellular Signalling
IS - 8
ER -