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Inhibition of MicroRNA‐429 Expression Mediates Angiotensin II‐induced Kidney Damages in Rats
Author(s) -
Wang Zhengchao,
Zhu Qing,
Wang Weili,
Li PinLan,
Hu Junping,
Li Ningjun
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.960.21
Subject(s) - endocrinology , transdifferentiation , angiotensin ii , medicine , renin–angiotensin system , chemistry , kidney , albumin , transfection , epithelial–mesenchymal transition , downregulation and upregulation , cell , biology , blood pressure , gene , biochemistry
MicroRNA (miR) 429 has been shown to inhibit epithelial‐to‐mesenchymal transition (EMT) and promote mesenchymal‐to‐epithelial transition (MET). The present study determined whether miR429 participated in angiotensin (ANG) II‐induced transdifferentiation and consequent fibrogenesis in renal cells. In NRK‐52E cells, a rat proximal tubular cell line, incubation of ANG II (1 nM) for 24 h significantly reduced the level of mir429 by 60% and meanwhile increased the protein levels of mechansymal markers α‐smooth muscle actin (α‐SMA) and fibroblast‐specific protein (FSP)‐1 by 3 fold and decreased epithelial marker E‐cadherin by 60%. In cells transfected with plasmids expressing mir429, ANG II‐induced changes in the above markers were abolished. Male Sprague‐Dawley rats were treated with chronic infusion of vehicle, ANG II (200 ng/kg/min) or ANG II + intrarenal transfection of lentivirus expressing mir429 for 12 days. The levels of mir429 in the kidneys were reduced by 75% in ANG II‐treated rats. The protein levels of α‐SMA, FSP‐1 and collagen I/III were much higher and E‐cadherin lower in the kidneys in ANG II‐treated rats than that in control. These changes were reversed in ANG II + mir429‐treated rats. The urinary albumin were 0.9±0.36 mg/Kg/24h in control, 2.8±0.28 mg/Kg/24h in ANG II‐treated and 1.2± 0.27 mg/Kg/24h in ANG II+mir429‐treated rats, respectively, at the end of experiment. There was no difference in the increases of blood pressure between ANG II‐ and ANG II+mir429‐ treated rats. These data suggested that ANG II produces transdifferentiation and fibrogenesis in renal cells via inhibiting mir429 expression and that miR429 protects against ANG II‐induced kidney damage. (Grant supports: NIH HL89563 and HL106042)