IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway.
Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury.
Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University Medical College, Shanghai 200092, China.
Zengbin
Z
Wu
Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University Medical College, Shanghai 200092, China.
Yang
Y
Yu
Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University Medical College, Shanghai 200092, China.
Lei
L
Niu
Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University Medical College, Shanghai 200092, China.
Aihua
A
Fei
Department of Emergency, Xinhua Hospital, Shanghai Jiaotong University Medical College, Shanghai 200092, China.
Shuming
S
Pan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C582202:MIRN429 microRNA, mouse; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D007334:Insulin-Like Growth Factor I