TGF-beta1-induced PINCH-1-ILK-alpha-parvin complex formation regulates mesangial cell proliferation and hypertrophy.
- Author:
Sung Min KIM
1
;
Nari KIM
;
Seoul LEE
;
Do Kyung KIM
;
Yu Min LEE
;
Seon Ho AHN
;
Ju Hung SONG
;
Bong Kyu CHOI
;
Chuanyue WU
;
Kyu Yong JUNG
Author Information
1. Department of Pharmacology, Wonkwang University School of Medicine, Iksan 570-749, Korea. wkuniv@wonkwang.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
alpha-parvin protein;
apoptosis;
cell proliferation;
hypertrophy;
integrin-linked kinase;
LIMS1 protein, human;
mesangial cells;
rat;
transforming growth factor beta1
- MeSH:
Animals;
*Cell Enlargement;
*Cell Proliferation;
Cells, Cultured;
Cyclin-Dependent Kinase Inhibitor p27/metabolism;
Cytoskeletal Proteins/*metabolism;
DNA-Binding Proteins/*metabolism;
Male;
Mesangial Cells/drug effects/*physiology;
Microfilament Proteins/*metabolism;
Phosphorylation;
Protein-Serine-Threonine Kinases/*metabolism;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Transforming Growth Factor beta1/*pharmacology;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Experimental & Molecular Medicine
2007;39(4):514-523
- CountryRepublic of Korea
- Language:English
-
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.
