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

Shanshan Wang, Jun Wang, Zengdi Zhang, Hongjun Miao

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Objective: Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Methods: 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. Results: 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. Conclusion: Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalJournal of Nephrology
Volume30
Issue number4
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017, Italian Society of Nephrology.

Keywords

  • MiRNA
  • Podocyte
  • Sepsis

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