Differences in transcriptional patterns of extracellular matrix, inflammatory, and myogenic regulatory genes in myofibroblasts, fibroblasts, and muscle precursor cells isolated ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-04-26

AUTHORS

Kevin A. Zwetsloot, Anders Nedergaard, Leigh T. Gilpin, Thomas E. Childs, Frank W. Booth

ABSTRACT

Aged skeletal muscle displays increased fibrosis and impaired regeneration. While it is not well characterized how skeletal muscle fibroblasts contribute to these phenomena, transforming growth factor-β1 (TGF-β1) and Delta/Notch signaling have been implicated to influence muscle regeneration. In this study, a unique combination of aging phenotypes is identified in differentiating fibroblasts (myofibroblasts), proliferating fibroblasts, and muscle precursor cells (MPCs) that characterize an impaired regenerative potential observed in aged skeletal muscle. Using a novel dual-isolation technique, that isolates fibroblasts and MPCs from the same rat skeletal muscle sample, and cell culture conditions of 5 % O2 and 5 % CO2, we report for the first time that myofibroblasts from 32-mo-old skeletal muscle, compared to 3-mo-old, display increased levels of mRNA for the essential extracellular matrix (ECM) genes, collagen 4α1 (83 % increase), collagen 4α2 (98 % increase), and laminin 2 (113 % increase), as well as increased levels of mRNA for the inflammatory markers, interleukin-6 (4.3-fold increase) and tumor necrosis factor α (3.2-fold increase), and TGF-β1 (84 % increase), whose protein controls proliferation and differentiation. Additionally, we demonstrate that proliferating fibroblasts from 32-mo-old skeletal muscle display increased levels of mRNA for the Notch ligand, Delta 1 (≥2.0-fold increase). Together, these findings suggest that increased expression of ECM and inflammatory genes in myofibroblasts from 32-mo-old skeletal muscle may contribute to the fibrogenic phenotype that impairs regeneration in aged skeletal muscle. Furthermore, we believe the novel dual-isolation technique developed here may be useful in studies that investigate communications among MPCs, fibroblasts, and myofibroblasts in skeletal muscle. More... »

PAGES

383-398

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10522-012-9382-7

DOI

http://dx.doi.org/10.1007/s10522-012-9382-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048161234

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22534744


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