PMID- 33294298 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221116 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 22 DP - 2020 Dec 4 TI - miR-363 Alleviates Detrusor Fibrosis via the TGF-beta1/Smad Signaling Pathway by Targeting Col1a2 in Rat Models of STZ-Induced T2DM. PG - 1142-1153 LID - 10.1016/j.omtn.2020.07.001 [doi] AB - Dysregulated expression of microRNAs (miRNAs or miRs) has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). However, their underlying role in the complication of detrusor fibrosis remains poorly understood. Therefore, this study aimed to examine the potential functional relevance of miR-363 in detrusor fibrosis of rats with streptozotocin (STZ)-induced T2DM through the predicted target gene collagen type I alpha 2 (Col1a2). Immunohistochemical analysis found an increase in the positive expression of collagen type III alpha 1 (Col3a1) and Col1a2 in detrusor tissues, where miR-363 expression was decreased. Next, gain- and loss-of-function experiments were performed to clarify the effects of miR-363 and Col1a2 on the activities of bladder detrusor cells. Of note, binding affinity between miR-363 and Col1a2 was verified by a dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Upregulated miR-363 inhibited Col1a2 expression, which led to increased expression of B-cell lymphoma 2 (Bcl-2) and Smad7 and accelerated cell viability, along with decreases in cell apoptosis and Col3a1, Bcl-2-associated X protein (Bax), transforming growth factor (TGF)-beta1, and Smad4 expressions. In conclusion, miR-363 upregulation reduces detrusor fibrosis in rats with STZ-induced T2DM through suppression of the TGF-beta1/Smad signaling pathway by targeting Col1a2. Therefore, our study provided further insights for the development of new therapeutic targets for T2DM. CI - (c) 2020. FAU - Li, Xue-Feng AU - Li XF AD - Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. FAU - Zhang, Shu-Hua AU - Zhang SH AD - Operation Room, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. FAU - Liu, Gui-Feng AU - Liu GF AD - Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. FAU - Yu, Shao-Nan AU - Yu SN AD - Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20200710 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 EIN - Mol Ther Nucleic Acids. 2022 Sep 02;29:787. PMID: 36159588 RIN - Mol Ther Nucleic Acids. 2022 Oct 26;30:323. PMID: 36381575 PMC - PMC7695978 OTO - NOTNLM OT - Col1a2 OT - TGF-beta1/Smad signaling pathway OT - detrusor fibrosis OT - microRNA-363 OT - type 2 diabetes mellitus EDAT- 2020/12/10 06:00 MHDA- 2020/12/10 06:01 PMCR- 2020/07/10 CRDT- 2020/12/09 06:14 PHST- 2020/06/10 00:00 [received] PHST- 2020/07/06 00:00 [accepted] PHST- 2020/12/09 06:14 [entrez] PHST- 2020/12/10 06:00 [pubmed] PHST- 2020/12/10 06:01 [medline] PHST- 2020/07/10 00:00 [pmc-release] AID - S2162-2531(20)30190-6 [pii] AID - 10.1016/j.omtn.2020.07.001 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2020 Jul 10;22:1142-1153. doi: 10.1016/j.omtn.2020.07.001. eCollection 2020 Dec 4.