title: TGF-beta1-induced PINCH-1-ILK-alpha-parvin complex formation regulates mesangial cell proliferation and hypertrophy.
abstract: TGF-beta1-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 alpha-parvin plays a pivotal role in the regulation of cell behavior such as cell proliferation and hypertrophy. We report here that PINCH-1-ILK-alpha-parvin (PIP) complex regulates the TGF-beta1-induced cell proliferation and hypertrophy in cultured rat GMCs. When GMCs were treated with TGF-beta1 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-beta1-treatment. TGF-beta1 induced early increase of caspase-3 activity. In GMCs incubated with TGF-beta1 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-beta1 for 1 day. TGF-beta1 induced early increase of phospho-p27(Kip1) (Thr 157) expression with subsequent decrease, and similar responses to TGF-beta1 were observed in the p38 phosphorylation (Thr 180/Thr 182). Taken together, TGF-beta1 differently regulates the PIP complex formation of GMCs in an incubation period-dependant fashion. The TGF-beta1-induced up- and down-regulation of the PIP complex formation likely contributes to the pleiotropic effects of TGF-beta1 on mesangial cell proliferation and hypertrophy through cellular localization of p27(Kip1) and alteration of Akt and p38 phosphorylation. TGF-beta1-induced alteration of the PIP complex formation may be importantly implicated in the development and progression of glomerular failure shown in several kidney diseases.
authors.affiliation: Department of Pharmacology, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Seoul
authors.initials: S
authors.lastname: Lee
authors.forename: Do Kyung
authors.initials: DK
authors.lastname: Kim
authors.forename: Yu Min
authors.initials: YM
authors.lastname: Lee
authors.forename: Seon Ho
authors.initials: SH
authors.lastname: Ahn
authors.forename: Ju Hung
authors.initials: JH
authors.lastname: Song
authors.forename: Bong Kyu
authors.initials: BK
authors.lastname: Choi
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.forename: Kyu Yong
authors.initials: KY
authors.lastname: Jung
mesh_terms: D000818:Animals; D049108:Cell Enlargement; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; D000099200:Scaffold Protein ILK; C493962:Cdkn1b protein, rat; C517887:Parva protein, rat