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肿瘤坏死因子-α抑制小鼠股四头肌来源细胞中的阿片肽受体表达。

TNF-α Suppresses Apelin Receptor Expression in Mouse Quadriceps Femoris-Derived Cells.

作者信息

Koyama Tomohisa, Uchida Kentaro, Itakura Makoto, Miyagi Masayuki, Tazawa Ryo, Inoue Gen, Fukushima Kensuke, Ohashi Yoshihisa, Tsukada Ayumi, Takaso Masashi

机构信息

Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku, Kitasato, Sagamihara City 252-0374, Kanagawa, Japan.

Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Minami-ku, Kitasato, Sagamihara City 252-0374, Kanagawa, Japan.

出版信息

Curr Issues Mol Biol. 2022 Jul 8;44(7):3146-3155. doi: 10.3390/cimb44070217.

Abstract

Expression of the apelin receptor, APJ, in skeletal muscle (SM) is known to decrease with age, but the underlying mechanism remains unclear. Increased tumor necrosis factor (TNF)-α levels are observed in SM with age and are associated with muscle atrophy. To investigate the possible interconnection between TNF-α elevation and APJ reduction with aging, we investigated the effect of TNF-α on APJ expression in cells derived from the quadriceps femoris of C57BL/6J mice. Expression of and in the quadriceps femoris was compared between 4- (young) and 24-month-old (old) C57BL/6J mice ( = 10 each) using qPCR. Additionally, APJ-positive cells and TNF-α protein were analyzed by flow cytometry and Western blotting, respectively. Further, quadricep-derived cells were exposed to 0 (control) or 25 ng/mL TNF-α, and the effect on expression was examined by qRT-PCR. expression and the ratio of APJ-positive cells among quadricep cells were significantly lower in old compared to young mice. In contrast, levels of mRNA and TNF-α protein were significantly elevated in old compared to young mice. Exposing young and old derived quadricep cells to TNF-α for 8 and 24 h caused levels to significantly decrease. TNF-α suppresses APJ expression in muscle cells in vitro. The increase in TNF-α observed in SM with age may induce a decrease in APJ expression.

摘要

已知阿片肽受体APJ在骨骼肌(SM)中的表达会随着年龄的增长而降低,但其潜在机制仍不清楚。随着年龄的增长,在骨骼肌中观察到肿瘤坏死因子(TNF)-α水平升高,且与肌肉萎缩有关。为了研究TNF-α升高与衰老过程中APJ减少之间可能存在的联系,我们研究了TNF-α对来自C57BL/6J小鼠股四头肌的细胞中APJ表达的影响。使用qPCR比较了4个月大(年轻)和24个月大(年老)的C57BL/6J小鼠(每组n = 10)股四头肌中APJ和TNF-α的表达。此外,分别通过流式细胞术和蛋白质免疫印迹法分析了APJ阳性细胞和TNF-α蛋白。进一步地,将股四头肌来源的细胞暴露于0(对照)或25 ng/mL的TNF-α中,并通过qRT-PCR检测其对APJ表达的影响。与年轻小鼠相比,年老小鼠股四头肌细胞中APJ的表达和APJ阳性细胞的比例显著降低。相反,与年轻小鼠相比,年老小鼠中TNF-α mRNA水平和TNF-α蛋白水平显著升高。将年轻和年老小鼠来源的股四头肌细胞暴露于TNF-α 8小时和24小时后,APJ水平显著降低。TNF-α在体外抑制肌肉细胞中APJ的表达。随着年龄增长在骨骼肌中观察到的TNF-α增加可能会导致APJ表达下降。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6db/9315797/1f2562ce0138/cimb-44-00217-g001.jpg

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