4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Genetic manipulation of CCN2/CTGF unveils cell-specific ECM-remodeling effects in injured skeletal muscle

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In skeletal muscle, extracellular matrix (ECM) remodeling can either support the complete regeneration of injured muscle or facilitate pathologic fibrosis and muscle degeneration. Muscular dystrophy (MD) is a group of genetic disorders that results in a progressive decline in muscle function and is characterized by the abundant deposition of fibrotic tissue. Unlike acute injury, where ECM remodeling is acute and transient, in MD, remodeling persists until fibrosis obstructs the regenerative efforts of diseased muscles. Thus, understanding how ECM is deposited and organized is critical in the context of muscle repair. Connective tissue growth factor (CTGF or CCN2) is a matricellular protein expressed by multiple cell types in response to tissue injury. Although used as a general marker of fibrosis, the cell type–dependent role of CTGF in dystrophic muscle has not been elucidated. To address this question, a conditional Ctgf myofiber and fibroblast-knockout mouse lines were generated and crossed to a dystrophic background. Only myofiber-selective inhibition of CTGF protected δ-sarcoglycan–null ( Sgcd −/− ) mice from the dystrophic phenotype, and it did so by affecting collagen organization in a way that allowed for improvements in dystrophic muscle regeneration and function. To confirm that muscle-specific CTGF functions to mediate collagen organization, we generated mice with transgenic muscle-specific overexpression of CTGF. Again, genetic modulation of CTGF in muscle was not sufficient to drive fibrosis, but altered collagen content and organization after injury. Our results show that the myofibers are critical mediators of the deleterious effects associated with CTGF in MD and acutely injured skeletal muscle.—Petrosino, J. M., Leask, A., Accornero, F. Genetic manipulation of CCN2/CTGF unveils cell-specific ECM-remodeling effects in injured skeletal muscle.

          Related collections

          Author and article information

          Journal
          FASEB J
          FASEB J
          fasebj
          fasebj
          The FASEB Journal
          Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
          0892-6638
          1530-6860
          February 2019
          14 September 2018
          14 September 2019
          : 33
          : 2
          : 2047-2057
          Affiliations
          [* ]Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA;
          []Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
          Author notes
          [1 ]Correspondence: Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, 473 W. 12th Ave., Columbus, OH 43210, USA. E-mail: federica.accornero@ 123456osumc.edu
          Article
          PMC6338641 PMC6338641 6338641 FJ_201800622RR
          10.1096/fj.201800622RR
          6338641
          30216109
          c2d366c9-95b6-47ab-a803-501cbdb70fe5
          © FASEB
          History
          : 29 March 2018
          : 20 August 2018
          Page count
          Figures: 5, Tables: 0, Equations: 1, References: 57, Pages: 11
          Categories
          Research
          Custom metadata
          v1

          muscle regeneration,muscular dystrophy,fibrosis
          muscle regeneration, muscular dystrophy, fibrosis

          Comments

          Comment on this article