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αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.

Titleαv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.
Publication TypeJournal Article
Year of Publication2017
AuthorsMurray IR, González 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
JournalNat Commun
Volume8
Issue1
Pagination1118
Date Published2017 Oct 24
ISSN2041-1723
Abstract

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.

DOI10.1038/s41467-017-01097-z
Alternate JournalNat Commun
PubMed ID29061963
PubMed Central IDPMC5653645
Grant List / / Wellcome Trust / United Kingdom
Publication institute
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