Effect of rosiglitazone on p38 mitogen-activated protein kinase pathway in polycystic kidney cyst-lining epithelial cells
JIA Jie-shuang, MEI Chang-lin, FU Li-li, DAI Bing, HU Hui-min
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Department of Nephrology, Nephrology Institute of PLA, Changzheng Hospital, the Second Military Medical University, Shanghai 200003, China
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History+
Received
Revised
Published
1900-01-01
1900-01-01
2009-06-15
Issue Date
2009-06-15
Abstract
Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells(PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone(10 μmol/L)+GW9662(10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phospho-p38(p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos and c-jun compared with control group(P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independent.
JIA Jie-shuang;MEI Chang-lin;FU Li-li;DAI Bing;HU Hui-min.
Effect of rosiglitazone on p38 mitogen-activated protein kinase pathway in polycystic kidney cyst-lining epithelial cells[J]. Chinese Journal of Nephrology, 2009, 25(6): 452-457.