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E3 连接酶 MuRF2 在骨骼肌成纤维细胞的功能能力中起着关键作用。

The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts.

机构信息

Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.

Faculdade de Ciências Aplicadas, UNICAMP, Limeira, SP, Brasil.

出版信息

Braz J Med Biol Res. 2019;52(9):e8551. doi: 10.1590/1414-431X20198551. Epub 2019 Aug 29.

Abstract

Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.

摘要

成纤维细胞是一种高度异质的细胞群体,存在于大量不同的组织中。这些细胞产生细胞外基质,对于维持结缔组织的结构完整性至关重要。成纤维细胞经常参与迁移和重塑,在细胞外基质中施加牵引力,这对于基质沉积和伤口愈合至关重要。此外,先前在原代成肌细胞上进行的研究表明,E3 连接酶 MuRF2 可能作为细胞骨架衔接蛋白发挥作用。在这里,我们假设 MuRF2 也在骨骼肌成纤维细胞中发挥功能作用。我们发现,骨骼肌成纤维细胞表达 MuRF2,其 siRNA 敲低促进了成纤维细胞迁移减少、聚合物化肌动蛋白在细胞边缘的积累以及磷酸化 Akt 表达的下调。我们的结果表明,MuRF2 通过 Akt 活性对于维持骨骼肌成纤维细胞中的肌动蛋白细胞骨架功能是必需的,并在骨骼肌组织中的细胞外基质重塑中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/155c/6720025/799fee52d92b/1414-431X-bjmbr-52-9-e8551-gf001.jpg

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