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血管周细胞 αv 整合素作为治疗骨骼肌纤维化的靶点。

Perivascular cell αv integrins as a target to treat skeletal muscle fibrosis.

机构信息

Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Anatomy of Domestic and Wild Animals Program, Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.

出版信息

Int J Biochem Cell Biol. 2018 Jun;99:109-113. doi: 10.1016/j.biocel.2018.04.002. Epub 2018 Apr 5.

Abstract

Fibrosis following injury leads to aberrant regeneration and incomplete functional recovery of skeletal muscle, but the lack of detailed knowledge about the cellular and molecular mechanisms involved hampers the design of effective treatments. Using state-of-the-art technologies, Murray et al. (2017) found that perivascular PDGFRβ-expressing cells generate fibrotic cells in the skeletal muscle. Strikingly, genetic deletion of αv integrins from perivascular PDGFRβ-expressing cells significantly inhibited skeletal muscle fibrosis without affecting muscle vascularization or regeneration. In addition, the authors showed that a small molecule inhibitor of αv integrins, CWHM 12, attenuates skeletal muscle fibrosis. From a drug-development perspective, this study identifies a new cellular and molecular target to treat skeletal muscle fibrosis.

摘要

损伤后的纤维化导致骨骼肌的异常再生和不完全的功能恢复,但由于缺乏对相关细胞和分子机制的详细了解,限制了有效治疗方法的设计。Murray 等人(2017 年)使用最先进的技术发现,血管周 PDGFRβ 表达细胞产生成纤维细胞,导致骨骼肌纤维化。引人注目的是,从血管周 PDGFRβ 表达细胞中剔除 αv 整合素显著抑制了骨骼肌纤维化,而不影响肌肉血管生成或再生。此外,作者还表明,αv 整合素的小分子抑制剂 CWHM 12 可减轻骨骼肌纤维化。从药物开发的角度来看,这项研究确定了一个新的细胞和分子靶点来治疗骨骼肌纤维化。

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