TY - JOUR
T1 - Identification and function of fibrocytes in skeletal muscle injury repair and muscular dystrophy
AU - Wang, Xingyu
AU - Zhao, Wanming
AU - Ransohoff, Richard M.
AU - Zhou, Lan
N1 - Funding Information:
This work was supported by National Institutes of Health Grant R01 AR059702 (to L.Z.).
Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - We identified and characterized the function of CD45+/collagen I+ fibrocytes in acutely injured skeletal muscle of wild-type (WT) and Ccr2-/- mice, and in quadriceps and diaphragm muscles of mdx5cv mice, a mouse model for Duchenne muscular dystrophy. Fibrocytes were not detected in peripheral blood of WT mice after acute muscle injury or mdx5cv mice. Fibrocytes were detected in acutely injured muscles and in mdx5cv quadriceps and diaphragm muscles. These cells expressed F4/80 and CCR2, and they were mostly Ly6Clo. They expressed a low level of collagens but a high level of profibrotic growth factors as compared with i.m. fibroblasts. Fibrocyte expression of collagens and profibrotic growth factors was not increased in Ccr2-/- mice as compared with WT controls. Fibrocyte expression of both proinflammatory and profibrotic cytokines was significantly higher in mdx5cv diaphragm than in mdx5cv quadriceps. In cocultures, fibrocytes from the mdx5cv diaphragm stimulated a higher level of fibroblast expression of extracellular matrix genes than did those from the mdx5cv quadriceps. Our findings suggest that i.m. fibrocytes most likely originate from infiltrating monocytes/macrophages and differentiate within injured muscles. They likely contribute to the normal muscle injury repair by producing growth factors. They do not appear to contribute to the persistent muscle fibrosis associated with poor injury repair in Ccr2-/- mice. However, they likely contribute to the persistent inflammation and progressive fibrosis in the mdx5cv diaphragm.
AB - We identified and characterized the function of CD45+/collagen I+ fibrocytes in acutely injured skeletal muscle of wild-type (WT) and Ccr2-/- mice, and in quadriceps and diaphragm muscles of mdx5cv mice, a mouse model for Duchenne muscular dystrophy. Fibrocytes were not detected in peripheral blood of WT mice after acute muscle injury or mdx5cv mice. Fibrocytes were detected in acutely injured muscles and in mdx5cv quadriceps and diaphragm muscles. These cells expressed F4/80 and CCR2, and they were mostly Ly6Clo. They expressed a low level of collagens but a high level of profibrotic growth factors as compared with i.m. fibroblasts. Fibrocyte expression of collagens and profibrotic growth factors was not increased in Ccr2-/- mice as compared with WT controls. Fibrocyte expression of both proinflammatory and profibrotic cytokines was significantly higher in mdx5cv diaphragm than in mdx5cv quadriceps. In cocultures, fibrocytes from the mdx5cv diaphragm stimulated a higher level of fibroblast expression of extracellular matrix genes than did those from the mdx5cv quadriceps. Our findings suggest that i.m. fibrocytes most likely originate from infiltrating monocytes/macrophages and differentiate within injured muscles. They likely contribute to the normal muscle injury repair by producing growth factors. They do not appear to contribute to the persistent muscle fibrosis associated with poor injury repair in Ccr2-/- mice. However, they likely contribute to the persistent inflammation and progressive fibrosis in the mdx5cv diaphragm.
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U2 - 10.4049/jimmunol.1601308
DO - 10.4049/jimmunol.1601308
M3 - Article
C2 - 27913649
AN - SCOPUS:85002244950
SN - 0022-1767
VL - 197
SP - 4750
EP - 4761
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -