HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/C661    most recent 00061.2007v2 00061.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Alexakis, C. Articles by Bou-Gharios, G. Search for Related Content PubMed PubMed Citation Articles by Alexakis, C. Articles by Bou-Gharios, G.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Implication of the satellite cell in dystrophic muscle fibrosis: a self-perpetuating mechanism of collagen overproduction

¹Muscle Cell Biology Group, Medical Research Council Clinical Science Centre, and ²Renal Medicine, Department of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom

Submitted 13 February 2007 ; accepted in final form 28 April 2007

Because of its mechanical function, skeletal muscle is heavily influenced by the composition of its extracellular matrix (ECM). Fibrosis generated by chronic damage, such as occurs in muscular dystrophies, is thus particularly disastrous in this tissue. Here, we examined the interrelationship between the muscle satellite cell and the production of collagen type I, a major component of fibrotic ECM, by using both C2C12, a satellite cell-derived cell line, and primary muscle satellite cells. In C2C12 cells, we found that expression of collagen type I mRNA decreases substantially during skeletal muscle differentiation. On a single-cell level, collagen type I and myogenin became mutually exclusive after 3 days in differentiation medium, whereas addition of collagen markedly suppressed differentiation of C2C12 cells. Primary cultures of satellite cells associated with isolated single fibers of the young (4 wk old) mdx dystrophic mouse and of C57BL/10ScSn wild-type controls expressed collagen type I and type III mRNA and protein. This pattern persisted in wild-type mice at all ages. But, curiously, in older (18-mo-old) mdx mice, although the myogenic cells continued to express type III collagen, type I expression became restricted to nonmyogenic cells. These cells typically constituted part of a cellular sheet surrounding the old mdx fibers. This combination of features strongly suggests that the progression to fibrosis in dystrophic muscle involves changes in the mechanisms controlling matrix production, which generates positive feedback that results in a reprogramming of myoblasts to a profibrotic function.

collagen type I; myogenin; muscle single fibers; Duchenne muscular dystrophy

This article has been cited by other articles:

				L. H. Jorgensen, S. J. Petersson, J. Sellathurai, D. C. Andersen, S. Thayssen, D. J. Sant, C. H. Jensen, and H. D. Schroder Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle J. Histochem. Cytochem., January 1, 2009; 57(1): 29 - 39. [Abstract] [Full Text] [PDF]

				K. D. Huebner, D. S. Jassal, O. Halevy, M. Pines, and J. E. Anderson Functional resolution of fibrosis in mdx mouse dystrophic heart and skeletal muscle by halofuginone Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1550 - H1561. [Abstract] [Full Text] [PDF]

				L. K. McLoon Focusing on fibrosis: halofuginone-induced functional improvement in the mdx mouse model of Duchenne muscular dystrophy Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1505 - H1507. [Full Text] [PDF]