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expression in renal tubular cells
1 Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: awazu{at}sc.itc.keio.ac.jp.
We investigated the expression of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). While the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 and phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. TGF-
was expressed in all tubular segments of DM coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24 to 72 h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB203580 or a MEK inhibitor PD98059 suppressed the HG-induced increases in protein content, [3H]-leucine incorporation, and the protein-to-DNA ratio. SB203580 or PD98059 also abolished the HG-stimulated expression of TGF- protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF- expression.
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