Format

Send to

Choose Destination
Nat Commun. 2017 Oct 24;8(1):1118. doi: 10.1038/s41467-017-01097-z.

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

Author information

1
Department of Trauma and Orthopaedics, University of Edinburgh, Chancellors Building, Little France Campus, Edinburgh, EH16 4TJ, UK.
2
BHF Centre for Vascular Regeneration & MRC Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
3
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
4
Center for World Health and Medicine, Saint Louis University, Edward A. Doisy Research Center, St. Louis, MO 63104, USA.
5
BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
6
Department of Pediatric Surgery, University of Texas McGovern Medical School, TX, 77030, USA.
7
Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine (IMM), The University of Texas Health Science Center at Houston (UT Health), TX, 77030, USA.
8
University of Bristol, Senate House, Tyndall Avenue, Bristol, BS8 1TH, UK.
9
Steadman Philippon Research Institute, Vail, CO 81657, USA.
10
Department of Orthopaedic Surgery, University of Texas, Medical School at Houston, Houston, TX 77030, USA.
11
BHF Centre for Vascular Regeneration & MRC Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK. bpeault@mednet.ucla.edu.
12
Orthopaedic Hospital Research Center and Broad Stem Cell Research Center, University of California, Los Angeles, CA 90024, USA. bpeault@mednet.ucla.edu.
13
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Neil.Henderson@ed.ac.uk.

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.

PMID:
29061963
PMCID:
PMC5653645
DOI:
10.1038/s41467-017-01097-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center