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KMID : 0620920070390040514
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Experimental & Molecular Medicine
2007 Volume.39 No. 4 p.514 ~ p.523
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TGF-β1-induced PINCH-1-ILK-α-parvin complex formation regulates mesangial cell proliferation and hypertrophy
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Kim Sung-Min
Song Ju-Hung
Kim Na-Ri
Lee Se-Oul
Kim Do-Kyung
Lee Yu-Min
Ahn Seon-Ho
Choi Bong-Kyu
ChuanYue Wu
Jung Kyu-Yong
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Abstract
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TGF-β1-induced glomerular mesangial cell (GMC) injury is a prominent characteristic of renal pathology in several kidney diseases, and a ternary protein complex consisting of PINCH-1, integrin-linked kinase (ILK) and α-parvin plays a pivotal role in the regulation of cell behavior such as cell proliferation and hypertrophy. We report here that PINCH-1-ILK-α-parvin (PIP) complex regulates the TGF-β1-induced cell proliferation and hypertrophy in cultured rat GMCs. When GMCs were treated with TGF-β1 for 1, 2 and 3 days, the PIP complex formation was up-regulated after 1 day, but it was down-regulated on day 2. Cell numbers were significantly elevated on day 2, but dramatically decreased on day 3. In contrast, a significant increase in cellular protein contents was observed 3 days after TGF-β1-treatment. TGF-β1 induced early increase of caspase-3 activity. In GMCs incubated with TGF-β1 for 2 days, cytosolic expression of p27Kip1 was dramatically reduced, but its nuclear expression was remarkably elevated. A significantly decreased expression of phospho-Akt (Ser 473) was observed in the cells treated with TGF-β1 for 1 day. TGF-β1 induced early increase of phospho- p27Kip1 (Thr 157) expression with subsequent decrease, and similar responses to TGF-β1 were observed in the p38 phosphorylation (Thr 180/Thr 182). Taken together, TGF-β1 differently regulates the PIP complex formation of GMCs in an incubation period- dependant fashion. The TGF-β1-induced up- and down-regulation of the PIP complex formation likely contributes to the pleiotropic effects of TGF-β1 on mesangial cell proliferation and hypertrophy through cellular localization of p27Kip1 and alteration of Akt and p38 phosphorylation. TGF-β1-induced alteration of the PIP complex formation may be importantly implicated in the development and progression of glomerular failure shown in several kidney diseases.
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KEYWORD
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α -parvin protein, apoptosis, cell proliferation, hypertrophy, integrin-linked kinase, LIMS1 protein, human, mesangial cells, rat, transforming growth factor β 1
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