Yonsei Med J.  2021 Mar;62(3):262-273. 10.3349/ymj.2021.62.3.262.

Long Non-Coding RNA RMRP Contributes to Sepsis-Induced Acute Kidney Injury

Affiliations
  • 1Department of Emergency, Affiliated Hospital of Nantong University, Nantong, China

Abstract

Purpose
This study aimed to explore the role of the long non-coding RNA (lncRNA) RNA component of mitochondrial RNAase P (RMRP) in sepsis-induced acute kidney injury (AKI).
Materials and Methods
Venous blood was collected from septic patients and healthy people. C57BL/6 mice who underwent cecal ligation and puncture (CLP) were used as in vivo models of septic AKI. Lipopolysaccharide (LPS)-induced HK-2 cells were employed as in vitro models of AKI. Flow cytometry analysis was conducted to detect cell apoptosis. Enzyme-linked immunosorbent assay and Western blot assays were used to detect levels of pro-inflammatory cytokines.
Results
RMRP was upregulated in sera from patients with AKI and in LPS-induced cells. Knockdown of RMRP inhibited cell apoptosis and reduced production of inflammatory factors in LPS-induced cells, as well as alleviated AKI in CLP mice. RMRP facilitated inflammation by activating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. We found that microRNA 206 (miR-206) binds with and is negatively regulated by RMRP: miR-206 directly targets the 3’ untranslated region of DEAD-box helicase 5 (DDX5) and negatively regulates DDX5 expression. By binding with miR-206, RMRP upregulated DDX5 expression. Rescue assays revealed that overexpression of DDX5 counteracted the effect of RMRP inhibition on cell apoptosis and inflammatory response in LPS-induced cells.
Conclusion
The lncRNA RMRP contributes to sepsis-induced AKI through upregulation of DDX5 in a miR-206 dependent manner and through activation of NLRP3 inflammasome. This novel discovery may provide a potential strategy for treating AKI.

Keyword

RMRP; miR-206; DDX5,; sepsis-induced AKI; NLRP3 inflammasome
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