Xia Zhang 1 , Zhongwei Huang 2 , Yan Wang 1 , Ting Wang 1 , Jingjing Li 1 , Peipei Xi 1 Show Affiliations »
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. © Copyright: Yonsei University College of Medicine 2021.
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. © Copyright: Yonsei University College of Medicine 2021.
Entities: CellLine
Chemical
Disease
Gene
Species
Keywords:
DDX5; NLRP3 inflammasome; RMRP; miR-206; sepsis-induced AKI
Year: 2021
PMID： 33635017 DOI： 10.3349/ymj.2021.62.3.262
Source DB: PubMed Journal: Yonsei Med J ISSN： 0513-5796 Impact factor: 2.759