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微小RNA-142通过靶向β-连环蛋白保护MC3T3-E1细胞免受高糖诱导的凋亡。

MicroRNA-142 protects MC3T3-E1 cells against high glucose-induced apoptosis by targeting β-catenin.

作者信息

Zheng Tiansheng, Ji Guanglin, Chen Jincai, Lai Jinliang, Liu Tong, Mo Jianwen, Jin Qi

机构信息

Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

出版信息

Exp Ther Med. 2020 Dec;20(6):125. doi: 10.3892/etm.2020.9253. Epub 2020 Sep 24.

DOI:10.3892/etm.2020.9253
PMID:33005251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7523292/
Abstract

Osteoporosis, characterized by decreased mineral density and bone mass, is triggered by various detrimental factors and often causes further complications, including fractures. Aberrant expression of microRNAs (miRs) has been associated with the pathogenesis of osteoporosis. Recently, miR-142 was reported to be downregulated in osteoblasts; however, the underlying mechanism of miR-142 in mediating the development of osteoporosis remains unclear. In the present study, high glucose induced the downregulation of miR-142 mRNA expression and promoted the apoptosis of MC3T3-E1 cells. miR-142-mimics significantly protected against high glucose-induced apoptosis, upregulated the expression levels of B-cell lymphoma 2 (Bcl-2) and downregulated the protein expression levels of β-catenin, Bcl-2 associated X (Bax) and caspase-3. Furthermore, β-catenin was identified as a direct target of miR-142 using luciferase reporter assays. Similar to the effects of miR-142 inhibitors, overexpression of β-catenin aggravated the apoptosis of MC3T3-E1 cells, as demonstrated by the upregulation of Bax and caspase-3, and the downregulation of Bcl-2 expression levels. In conclusion, miR-142 protects MC3T3-E1 cells against high glucose-induced apoptosis by targeting β-catenin.

摘要

骨质疏松症的特征是矿物质密度和骨量降低,由多种有害因素引发,且常导致包括骨折在内的进一步并发症。微小RNA(miR)的异常表达与骨质疏松症的发病机制有关。最近,有报道称miR-142在成骨细胞中表达下调;然而,miR-142介导骨质疏松症发展的潜在机制仍不清楚。在本研究中,高糖诱导miR-142 mRNA表达下调,并促进MC3T3-E1细胞凋亡。miR-142模拟物显著保护细胞免受高糖诱导的凋亡,上调B细胞淋巴瘤2(Bcl-2)的表达水平,并下调β-连环蛋白、Bcl-2相关X蛋白(Bax)和半胱天冬酶-3的蛋白表达水平。此外,通过荧光素酶报告基因检测确定β-连环蛋白是miR-142的直接靶点。与miR-142抑制剂的作用类似,β-连环蛋白的过表达加重了MC3T3-E1细胞的凋亡,表现为Bax和半胱天冬酶-3上调,以及Bcl-2表达水平下调。总之,miR-142通过靶向β-连环蛋白保护MC3T3-E1细胞免受高糖诱导的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/e036fc944434/etm-20-06-09253-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/b5999584f1cb/etm-20-06-09253-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/f91b9fd7d35a/etm-20-06-09253-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/27b045be48f6/etm-20-06-09253-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/e036fc944434/etm-20-06-09253-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/b5999584f1cb/etm-20-06-09253-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/f91b9fd7d35a/etm-20-06-09253-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/27b045be48f6/etm-20-06-09253-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0248/7523292/e036fc944434/etm-20-06-09253-g03.jpg

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