Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis

Journal of Nephrology
Shanshan WangHongjun Miao

Abstract

Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study sugg...Continue Reading

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Citations

Jan 23, 2019·The Journal of Pharmacy and Pharmacology·Jun ShenGuanghui Pan
Dec 22, 2019·Journal of Nephrology·Bo-Yang XuHong Zhang
Jun 10, 2020·IUBMB Life·Rasoul MirzaeiRasoul Yousefimashouf
Jul 19, 2018·Journal of Nephrology·Alieh GholaminejadMohammad Gholami Fesharaki
Aug 23, 2019·Acta Cirúrgica Brasileira·Yezhou ShenJian Zhang
Oct 1, 2019·Journal of the Chinese Medical Association : JCMA·Yanjun QinCaiyan Zhao

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