ERK and p38 mediate high-glucose-induced hypertrophy and TGF-beta expression in renal tubular cells.
We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although 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. Transforming growth factor (TGF)-beta 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 SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-beta 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-beta expression.
Fujita
Hisayo
H
Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Omori
Sayu
S
Ishikura
Kenji
K
Hida
Mariko
M
Awazu
Midori
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006984:Hypertrophy; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D018374:LLC-PK1 Cells; D007930:Leucine / Q000493:pharmacokinetics; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014316:Tritium; D048051:p38 Mitogen-Activated Protein Kinases
D007004:Hypoglycemic Agents; D007328:Insulin; D016212:Transforming Growth Factor beta; D014316:Tritium; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007930:Leucine; D005947:Glucose