[OP.4D.02] ADIPONECTIN-MEDIATED EPITHILIAL AUTOPHAGY ATTENUATES HYPERTENSIVE RENAL FIBROSIS

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Abstract

Objective:

Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice.

Design and method:

Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release). Fourteen days after DOCA-salt infusion, immunostaining, Western blot and Transmission electron microscope were performed to detect autophagy and renal fibrosis. In vitro, APN treated HK-2 renal epithelial cell was infected with mGFP-RFP-LC3 adenovirus to detect autophagosomes.

Results:

APNKO and WT mice both developed equally high blood pressure levels. However, APNKO mice developed more severe renal fibrosis and less compared with WT mice. This finding was demonstrated by the up-regulation of collagen I, alpha -smooth muscle actin, and decreased E-cadherin in APNKO mice. Moreover, there were substantially fewer autophagosomes and LC3 psotive epithelial cells in the kidney of APNKO DOCA-salt mice. Additional in vitro studies also revealed that recombinant APN treatment inhibited aldosterone-induced EMT, induced autophagy with enhanced 5’-monophosphate-activated protein kinase (AMPK) phosphorylation. In contrast, APN-induced autophagy and enhanced E-cadherin expression was diminished by autophagy inhibitor chloroquine or Compound C, an inhibitor of AMPK pathway.αα

Conclusions:

Our study indicates that APN activates epithelial autophagy through the AMPK signaling pathway and suppresses aldosterone-induced EMT, thereby reducing DOCA-salt hypertensionI-induced renal fibrosis.

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