[p38 MAPK mediates high glucose-induced renal tubular epithelial-mesenchymal transition.].
The aim of the present study was to investigate the role of p38 MAPK in the renal tubular epithelial-mesenchymal transition (TEMT) induced by high glucose. In in vivo study, the rats were randomly divided into control (C), diabetes mellitus (DM) and insulin-treated DM groups. Immunohistochemical staining and Western blot were employed to determine the expression of p38 MAPK and p-p38 MAPK protein in renal cortex of rats. In in vitro study, primary renal tubular epithelial cells (PTECs) were cultured with normal glucose (5.5 mmol/L), high glucose (20 mmol/L D-glucose), high osmolality (20 mmol/L D-mannitol) and SB202190 (a p38 MAPK inhibitor) plus high glucose respectively for 72 h. The expressions of p38 MAPK, p-p38 MAPK, Snail1, transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) and E-cadherin protein and mRNA were detected by immunocytochemical staining, Western blot and RT-PCR. The p38 MAPK and p-p38 MAPK were specifically upregulated by high glucose in both in vivo and in vitro studies. The p38 MAPK activation was abolished by insulin controlling hyperglycemia to normal level in DM rats and inhibited dramatically by SB202190 in high glucose-cultured PTECs. The protein and mRNA of alpha-SMA were markedly increased in PTECs cultured with high glucose and were 12-fold and 8-fold respectively over that in the normal glucose, which were significantly suppressed by SB202190. SB202190 down-regulated the high glucose-induced Snail1 protein expression in PETCs, and restored partly the depression of E-cadherin protein and mRNA. These results suggest that p38 MAPK mediates high glucose-induced TEMT via transcription factor Snail1.
Fang
Kai-Yun
KY
Department of Pathophysiology, Guiyang Medical College, Guiyang, China.
Shi
Ming-Juan
MJ
Xiao
Ying
Y
Gui
Hua-Zhen
HZ
Guo
Bing
B
Zhang
Guo-Zhong
GZ
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005947:Glucose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D005947:Glucose; D007093:Imidazoles; D007328:Insulin; D011725:Pyridines; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C000604450:Snai2 protein, rat; C498862:Acta2 protein, rat; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole