Abstract
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 p27(Kip1) 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-p27(Kip1) (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 p27(Kip1) 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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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Kim, S., Kim, N., Lee, S. et al. TGF-β1-induced PINCH-1-ILK-α-parvin complex formation regulates mesangial cell proliferation and hypertrophy. Exp Mol Med 39, 514–523 (2007). https://doi.org/10.1038/emm.2007.57
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DOI: https://doi.org/10.1038/emm.2007.57
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