Date: Tuesday, June 4, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: Room 313
*Purpose: Previously, we found up-regulation of miR-20a after kidney ischemia reperfusion (I/R) injury and may serves as a protector; however, its specific mechanism remains unclear.Autophagy is also a key regulator of kidney I/R injury. Thus, we investigate whether miR-20a can regulate autophagy in renal I/R injury.
*Methods: An I/R-induced mice I/R injury model and a hypoxia-induced HK-2 cell model were used.The concentration of renal function serum creatinine, blood urea nitrogen were mesured. miR-20a agomir or siRNA were used to up-and down regulate the expression of miR-20a. Cell apoptosis was evaluated by flow cytometry and autophagy level was assessed by autophagy marker and autophagy flux.
*Results: MiR-20a up-regulated in vivo but down-regulated in vitro. In vitro, miR-20a agomir, an miR-20a mimic, can greatly reduced the apoptosis by decreasing the autophagy level. miR-20a directly inhibited the expression of PTEN and BIM and attenuated apoptosis and autophagy, similar to the effect of Chloroquine, a pharmacological inhibitor of autophagy. Mechanistically, the anti-autophagic and anti-apoptotic effect of miR-20a can be reversed by AKT-siRNA, a down-stream protein of PTEN and BIM. Further, we identified the Akt phosphorated Beclin1 was up-regulated, may play the direct anti-autophagic effect. In addition, the administration of miR-20a agomir can greatly inhibited the autophagy level and apoptosis, leading to significantly improved renal function recovery and tissue injury in mice IRI model.
*Conclusions: Thus, our results establish a renoprotective role of miR-20a in renal I/R injury where it may interfere with autophagy by targeting PTEN and BIM.
To cite this abstract in AMA style:Lin T, Song T, Jiang Y, Liu J, Wang Z, Li L, Huang Z, Fan Y, Wang X. miR-20a Inhibits Autophagy by Targeting AKT and BIM in Renal Reperfusion Injury [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/mir-20a-inhibits-autophagy-by-targeting-akt-and-bim-in-renal-reperfusion-injury/. Accessed November 15, 2019.
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