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

被引:18
|
作者
Prazeres, Pedro H. D. M. [1 ]
Turquetti, Anaelise O. M. [2 ]
Azevedo, Patrick O. [1 ]
Barreto, Rodrigo S. N. [2 ]
Miglino, Maria A. [2 ]
Mintz, Akiva [3 ]
Delbono, Osvaldo [4 ]
Birbrair, Alexander [1 ,2 ,3 ]
机构
[1] Univ Fed Minas Gerais, Dept Pathol, Belo Horizonte, MG, Brazil
[2] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Surg, Anat Domest & Wild Anim Program, Sao Paulo, SP, Brazil
[3] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10027 USA
[4] Wake Forest Sch Med, Dept Internal Med Gerontol, Winston Salem, NC USA
基金
美国国家卫生研究院;
关键词
Perivascular cells; Skeletal muscle; Fibrosis; Integrins; PDGFR beta; HUMAN BRAIN PERICYTES; PULMONARY-FIBROSIS; ENDOTHELIAL-CELLS; BARRIER INTEGRITY; MYOFIBROBLASTS; COLLAGEN; REGENERATION; EXPRESSION; PATHWAY; INJURY;
D O I
10.1016/j.biocel.2018.04.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 PDGFR beta-expressing cells generate fibrotic cells in the skeletal muscle. Strikingly, genetic deletion of alpha v integrins from perivascular PDGFR beta-expressing cells significantly inhibited skeletal muscle fibrosis without affecting muscle vascularization or regeneration. In addition, the authors showed that a small molecule inhibitor of alpha v 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.
引用
收藏
页码:109 / 113
页数:5
相关论文
共 50 条
  • [1] Role of αν integrins on perivascular mesenchymal cells in regulation of skeletal and cardiac muscle fibrosis
    Murray, Iain
    Gonzalez, Zaniah
    Baily, James
    Smith, Jamie
    Thomson, Alexandra
    Greenhalgh, Stephen
    Dobbie, Ross
    Kendall, Tim
    Gray, Gillian
    Griggs, David
    Ruminski, Peter
    Simpson, Hamish
    Iredale, John
    Peault, Bruno
    Henderson, Neil
    [J]. LANCET, 2017, 389 : 13 - 13
  • [2] αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis
    Murray, I. R.
    Gonzalez, Z. N.
    Baily, J.
    Dobie, R.
    Wallace, R. J.
    Mackinnon, A. C.
    Smith, J. R.
    Greenhalgh, S. N.
    Thompson, A. I.
    Conroy, K. P.
    Griggs, D. W.
    Ruminski, P. G.
    Gray, G. A.
    Singh, M.
    Campbell, M. A.
    Kendall, T. J.
    Dai, J.
    Li, Y.
    Iredale, J. P.
    Simpson, H.
    Huard, J.
    Peault, B.
    Henderson, N. C.
    [J]. NATURE COMMUNICATIONS, 2017, 8
  • [3] αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis
    I. R. Murray
    Z. N. Gonzalez
    J. Baily
    R. Dobie
    R. J. Wallace
    A. C. Mackinnon
    J. R. Smith
    S. N. Greenhalgh
    A. I. Thompson
    K. P. Conroy
    D. W. Griggs
    P. G. Ruminski
    G. A. Gray
    M. Singh
    M. A. Campbell
    T. J. Kendall
    J. Dai
    Y. Li
    J. P. Iredale
    H. Simpson
    J. Huard
    B. Péault
    N. C. Henderson
    [J]. Nature Communications, 8
  • [4] Integrins as a drug target in liver fibrosis
    Rahman, Syedia R.
    Roper, James A.
    Grove, Jane, I
    Aithal, Guruprasad P.
    Pun, K. Tao
    Bennett, Andrew J.
    [J]. LIVER INTERNATIONAL, 2022, 42 (03) : 507 - 521
  • [5] αvβ3 and αvβ5 integrins and their role in muscle precursor cell adhesion
    Sinanan, Andrea C. M.
    Machell, Jon R. A.
    Wynne-Hughes, G. Trevor
    Hunt, Nigel P.
    Lewis, Mark R.
    [J]. BIOLOGY OF THE CELL, 2008, 100 (08) : 465 - 477
  • [6] Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
    Matthijs K. C. Hesselink
    Vera Schrauwen-Hinderling
    Patrick Schrauwen
    [J]. Nature Reviews Endocrinology, 2016, 12 : 633 - 645
  • [7] Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
    Hesselink, Matthijs K. C.
    Schrauwen-Hinderling, Vera
    Schrauwen, Patrick
    [J]. NATURE REVIEWS ENDOCRINOLOGY, 2016, 12 (11) : 633 - 645
  • [8] Integrins: Redundant or important players in skeletal muscle?
    Mayer, U
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (17) : 14587 - 14590
  • [9] αv integrins: key regulators of tissue fibrosis
    Conroy, Kylie P.
    Kitto, Laura J.
    Henderson, Neil C.
    [J]. CELL AND TISSUE RESEARCH, 2016, 365 (03) : 511 - 519
  • [10] αv integrins: key regulators of tissue fibrosis
    Kylie P. Conroy
    Laura J. Kitto
    Neil C. Henderson
    [J]. Cell and Tissue Research, 2016, 365 : 511 - 519