αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.
αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.
复制标题
DOI：
10.1038/s41467-017-01097-z
复制
发表时间：
2017-10-24
影响因子：
16.6
通讯作者：
Henderson NC
中科院分区：
文献类型：
--
作者：
Murray IR;Gonzalez ZN;Baily J;Dobie R;Wallace RJ;Mackinnon AC;Smith JR;Greenhalgh SN;Thompson AI;Conroy KP;Griggs DW;Ruminski PG;Gray GA;Singh M;Campbell MA;Kendall TJ;Dai J;Li Y;Iredale JP;Simpson H;Huard J;Péault B;Henderson NC
表达血小板衍生生长因子受体β (PDGFRβ)的间充质细胞在肝脏和肾脏等器官纤维化中起重要作用。在这里，我们表明PDGFRβ+细胞通过依赖于αv整合素的机制促进骨骼肌和心脏纤维化。PDGFRβ+细胞中αv整合素缺失的小鼠免受心脏毒素和撕裂诱导的骨骼肌纤维化和血管紧张素ii诱导的心脏纤维化。此外，αv整合素的小分子抑制剂可减轻骨骼肌和心肌的纤维化，即使预先建立，并改善骨骼肌功能。αv整合素阻断也可降低原代人骨骼肌和心脏PDGFRβ+细胞中TGFβ的活化，提示αv整合素抑制剂可有效治疗和预防多种肌肉纤维化。组织纤维化的机制尚不清楚。作者表明，表达PDGFRβ的间充质细胞通过涉及αv整合素的机制介导骨骼肌和心脏的纤维化，αv整合素的抑制剂可减轻小鼠的纤维化反应。
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFβ activation in primary human skeletal muscle and cardiac PDGFRβ+ cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses. The mechanisms underlying tissue fibrosis are unclear. The authors show that mesenchymal cells expressing PDGFRβ mediate fibrosis in skeletal muscle and heart via a mechanism involving αv integrin, and that inhibitors of αv integrins attenuate fibrotic responses in mice.
登录
查看更多内容
影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
23.9
作者：
Guimarães-Camboa N;Cattaneo P;Sun Y;Moore-Morris T;Gu Y;Dalton ND;Rockenstein E;Masliah E;Peterson KL;Stallcup WB;Chen J;Evans SM
通讯作者：
Evans SM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.9
作者：
BABAI, F;MUSEVIAGHDAM, J;GABBIANI, G
通讯作者：
GABBIANI, G
影响因子：
4.9
作者：
Mann CJ;Perdiguero E;Kharraz Y;Aguilar S;Pessina P;Serrano AL;Muñoz-Cánoves P
通讯作者：
Muñoz-Cánoves P