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整合素 α1 亚基及其与高脂肪饮食对骨骼肌和肌腱细胞外基质合成的影响。

Influence of the integrin alpha-1 subunit and its relationship with high-fat diet upon extracellular matrix synthesis in skeletal muscle and tendon.

机构信息

Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital, Nielsine Nielsenvej 11, 2400, Copenhagen NV, Denmark.

Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Cell Tissue Res. 2020 Jul;381(1):177-187. doi: 10.1007/s00441-020-03184-y. Epub 2020 Feb 28.

Abstract

Integrins are important for mechanosensation in tissue and play, together with nutrition, a role in regulating extracellular matrix (ECM) in skeletal muscle and tendon. Integrin receptors are dimers that consist of an α and β subunit and bridge extracellular and intracellular signals. The present study investigates whether the deletion of the integrin receptor α subunit influences collagen and other matrix proteins in the musculotendinous tissue and whether it causes any compensatory changes in other integrin subunits in C57BL/6J mice. In addition, we study whether a high-fat diet (HFD) influences these responses in muscle or tendon. Mice on a HFD had a higher number of non-enzymatic cross-links in skeletal muscle ECM and increased gene expression of collagen and other extracellular matrix proteins. In contrast to gene expression, total collagen protein content was decreased by HFD in the muscle with no change in tendon. Integrin α subunit knockout resulted in a decrease of collagen type I and III, TGF-β1 and IGF-1 gene expression in muscle of HFD mice but did not affect total collagen protein compared with wild-type (WT) littermates in either muscle or tendon. There was no compensatory increase in the genes that express other integrin subunits. In conclusion, HFD induced a significant increase in expression of ECM genes in muscle. On the protein level, HFD resulted in a lower collagen content in muscle. Tendons were unaffected by the diet. Deletion of the integrin α subunit did not affect collagen protein or gene expression in muscle or tendon.

摘要

整合素对于组织和运动中的机械感觉很重要,与营养一起,在调节骨骼肌和肌腱中的细胞外基质(ECM)方面发挥作用。整合素受体是由一个α和β亚基组成的二聚体,连接细胞外和细胞内信号。本研究调查了整合素受体α亚基的缺失是否会影响肌肉肌腱组织中的胶原和其他基质蛋白,以及它是否会导致 C57BL/6J 小鼠中其他整合素亚基发生任何代偿性变化。此外,我们还研究了高脂肪饮食(HFD)是否会影响肌肉或肌腱中的这些反应。高脂肪饮食的小鼠骨骼肌 ECM 中非酶交联的数量增加,胶原和其他细胞外基质蛋白的基因表达增加。与基因表达相反,高脂肪饮食导致肌肉中总胶原蛋白含量降低,而肌腱中没有变化。与野生型(WT)同窝仔相比,整合素α亚基敲除导致高脂肪饮食小鼠肌肉中胶原 I 和 III、TGF-β1 和 IGF-1 基因表达减少,但对肌肉或肌腱中的总胶原蛋白没有影响。表达其他整合素亚基的基因没有代偿性增加。总之,高脂肪饮食诱导肌肉中 ECM 基因表达显著增加。在蛋白质水平上,高脂肪饮食导致肌肉中胶原含量降低。肌腱不受饮食影响。整合素α亚基的缺失不影响肌肉或肌腱中的胶原蛋白或基因表达。

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