PMID- 36440854 OWN - NLM STAT- MEDLINE DCOM- 20230202 LR - 20230216 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 324 IP - 2 DP - 2023 Feb 1 TI - LncRNA NEAT1 accelerates renal fibrosis progression via targeting miR-31 and modulating RhoA/ROCK signal pathway. PG - C292-C306 LID - 10.1152/ajpcell.00382.2021 [doi] AB - Renal fibrosis is the final pathway for chronic kidney disease to end-stage renal failure. Noncoding RNAs have been reported to play a crucial role in renal fibrosis. Here, the effects of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) and miR-31 on renal fibrosis and their regulatory mechanism were evaluated. RT-qPCR was used to assess NEAT1, miR-31, and RhoA levels. Western blot was performed to analyze the expression of fibrosis markers, RhoA, rho-related kinase (ROCK1), and connective tissue growth factor (CTGF). RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and luciferase reporter assays verified the interaction between miR-31 and NEAT1 or RhoA. Renal fibrosis and injury were observed by Masson and hematoxylin and eosin (H&E) staining. The expression level of inflammatory cytokines was detected by ELISA. Immunohistochemistry (IHC) was performed to examine the expression levels of alpha-smooth muscle actin (alpha-SMA) and RhoA in renal tissues. We showed that NEAT1 was highly expressed, whereas miR-31 was decreased in renal fibrosis. NEAT1 was found to directly bind miR-31 to positively regulate RhoA expression. Furthermore, NEAT1 silencing inhibited renal fibrosis and inflammation and suppressed the RhoA/ROCK1 signaling pathway. However, knockdown of miR-31 could reverse these effects. NEAT1 silencing or overexpression of miR-31 alleviated renal fibrosis in vivo. In conclusion, NEAT1 accelerates renal fibrosis progression via negative regulation of miR-31 and the activation of RhoA/ROCK1 pathway, thereby upregulating the expression level of CTGF, providing a theoretical basis for treatment and prognostic evaluation of renal fibrosis. FAU - Chen, Yan AU - Chen Y AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Huang, Chong AU - Huang C AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Duan, Zhi-Bin AU - Duan ZB AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Chen, Yan-Xia AU - Chen YX AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Xu, Cheng-Yun AU - Xu CY AUID- ORCID: 0000-0003-3747-3728 AD - Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221128 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 124671-05-2 (RHOA protein, human) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - EC 2.7.11.1 (ROCK1 protein, human) RN - EC 2.7.11.1 (rho-Associated Kinases) RN - 0 (MIRN31 microRNA, human) SB - IM MH - Humans MH - *MicroRNAs/genetics/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Fibrosis MH - *Kidney Diseases MH - Signal Transduction MH - Apoptosis MH - rhoA GTP-Binding Protein/genetics/metabolism MH - rho-Associated Kinases/genetics/metabolism OTO - NOTNLM OT - RhoA/ROCK1 signal pathway OT - lncRNA NEAT1 OT - miR-31 OT - renal fibrosis EDAT- 2022/11/29 06:00 MHDA- 2023/02/03 06:00 CRDT- 2022/11/28 08:23 PHST- 2022/11/29 06:00 [pubmed] PHST- 2023/02/03 06:00 [medline] PHST- 2022/11/28 08:23 [entrez] AID - 10.1152/ajpcell.00382.2021 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C292-C306. doi: 10.1152/ajpcell.00382.2021. Epub 2022 Nov 28.