• Xia Zhang, Zhongwei Huang, Yan Wang, Ting Wang, Jingjing Li, and Peipei Xi.
• Department of Emergency, Affiliated Hospital of Nantong University, Nantong, China.
• Yonsei Med. J. 2021 Mar 1; 62 (3): 262273262-273.

PurposeThis 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 MethodsVenous 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.ResultsRMRP 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.ConclusionThe 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.© Copyright: Yonsei University College of Medicine 2021.

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