title: Identification and Function of Fibrocytes in Skeletal Muscle Injury Repair and Muscular Dystrophy.
abstract: 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 mdx5cvmice, a mouse model for Duchenne muscular dystrophy. Fibrocytes were not detected in peripheral blood of WT mice after acute muscle injury or mdx5cvmice. Fibrocytes were detected in acutely injured muscles and in mdx5cvquadriceps and diaphragm muscles. These cells expressed F4/80 and CCR2, and they were mostly Ly6CloThey 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 mdx5cvdiaphragm than in mdx5cvquadriceps. In cocultures, fibrocytes from the mdx5cvdiaphragm stimulated a higher level of fibroblast expression of extracellular matrix genes than did those from the mdx5cvquadriceps. 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 mdx5cvdiaphragm.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and.
authors.forename: Wanming
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Neuroimmunology, Biogen, Cambridge, MA 02142.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and lan.zhou@mssm.edu.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003964:Diaphragm / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000276:immunology / Q000473:pathology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; C515335:Ccr2 protein, mouse; D024042:Collagen Type I; D016207:Cytokines; D018836:Inflammation Mediators; D054390:Receptors, CCR2; C036763:monocyte-macrophage differentiation antigen; D017493:Leukocyte Common Antigens