Zhen-wu-tang attenuates Adriamycin-induced nephropathy via regulating AQP2 and miR-92b

Biomed Pharmacother. 2019 Jan:109:1296-1305. doi: 10.1016/j.biopha.2018.10.146. Epub 2018 Nov 9.

Abstract

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia and edema. The disorder of sodium and water metabolism is a critical mechanism regulating the origination and progression of NS. Zhen-wu-tang (ZWT) has been traditionally used to treat edema disease in China and Japan. The present study was carried out to assess the protective effect of ZWT in Adriamycin-induced (ADR) NS rats and investigate the potential anti-NS mechanisms of ZWT. We found that ZWT treatment ameliorate impaired kidney function and regulate water balance of kidney. Importantly, ZWT increased the expression of Aquaporin-2 (AQP2) which play key roles in maintaining body water homeostasis. Additionally, we determined miRNAs expression patterns in NS rats. Using bioinformatics prediction and miR-92b mimic or inhibitor in vitro, we identified miR-92b as a possible modulator of AQP2. Also we found that ZWT can decrease the expression of miR-92b and reverse the effect of miR-92b on AQP2 in vitro. We further demonstrated that miR-92b directly regulated AQP2 expression by targeting 3'-UTR of AQP2. These finding suggest that ZWT may reduce renal edema in Adriamycin-induced nephropathy via regulating AQP2 and miR-92b.

Keywords: Aquaporin; Edema; MicroRNA; Nephrotic syndrome; Zhen-wu-tang.

MeSH terms

  • Animals
  • Aquaporin 2 / metabolism*
  • China
  • Doxorubicin / pharmacology*
  • Drugs, Chinese Herbal / pharmacology*
  • Japan
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Aqp2 protein, rat
  • Aquaporin 2
  • Drugs, Chinese Herbal
  • MIRN92 microRNA, rat
  • MicroRNAs
  • zhen-wu-tang
  • Doxorubicin