title: Chemokine receptor CCR2 involvement in skeletal muscle regeneration.
abstract: Chemokines, signaling through the CCR2 receptor, are highly expressed in injured skeletal muscle. Their target specificity depends on the cellular expression of the specific receptors. Here we demonstrate that, in freeze-injured muscle, CCR2 co-localized with Mac-3, a marker of activated macrophages as well as with myogenin, a marker of activated muscle precursor cells. The degeneration/regeneration process in skeletal muscle of CCR2-/- and wild-type mice was not significantly different at day 3. However in contrast to the regenerated muscle of the wild-type mice, the muscle from CCR2-/- mice was characterized by impaired regeneration, inflammation, and fibrotic response at day 14, increased fat infiltration, fibrosis, and calcification at day 21, and impaired strength recovery until at least 28 days post-injury. Consistently, the increased expression of Mac-1 and TNF-alpha was prolonged in the injured muscle of CCR2-/- mice. The expression pattern of the myogenic factors MyoD and myogenin was similar for both types of mice, while NCAM, which is associated with the initiation of fusion of muscle precursor cells, was more increased in the injured muscle of CCR2-/- mice. In conclusion, the study delineates that signaling through CCR2 is involved in muscle precursor cell activities necessary for complete and rapid regeneration of injured skeletal muscle.
authors.affiliation: Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Warren
authors.forename: Tracy
authors.initials: T
authors.lastname: Hulderman
authors.forename: Dawn
authors.initials: D
authors.lastname: Mishra
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Lyndell
authors.initials: L
authors.lastname: Millecchia
authors.forename: Laura
authors.initials: L
authors.lastname: O'Farrell
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Petia P
authors.initials: PP
authors.lastname: Simeonova
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D004396:Coloring Agents; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D005615:Freezing; D015870:Gene Expression; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics; D018008:Myogenin / Q000032:analysis / Q000235:genetics; D009220:Myositis / Q000209:etiology / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors
chemical_list: C515335:Ccr2 protein, mouse; D004396:Coloring Agents; D016177:Macrophage-1 Antigen; D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine