| First Author | Zhao W | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 1 | Pages | 35-46 |
| PubMed ID | 27655900 | Mgi Jnum | J:321061 |
| Mgi Id | MGI:6859525 | Doi | 10.1096/fj.201600619R |
| Citation | Zhao W, et al. (2017) CCR2 deficiency does not provide sustained improvement of muscular dystrophy in mdx5cv mice. FASEB J 31(1):35-46 |
| abstractText | Genetic ablation or pharmacologic inhibition of CC chemokine receptor type 2 (CCR2) reduced macrophage (MP) infiltration and improved muscle pathology and function in mdx diaphragm muscle at early stages. We addressed whether CCR2 deficiency resulted in sustained improvement of mdx(5cv)-Ccr2(-/-) diaphragm. Compared to mdx(5cv) controls, CCR2 deficiency in mdx(5cv)-Ccr2(-/-) mice markedly reduced intramuscular Ly6C(hi) MPs at all stages, but it reduced Ly6C(low) MPs only at early stages (4 and 9 wk). CCR2 deficiency reduced quadriceps and diaphragm muscle damage and fibrosis at 14 wk but not at 6 mo, and it improved diaphragm muscle regeneration and respiratory function at 14 wk but not at 6 mo. Intramuscular MPs in mdx(5cv)-Ccr2(-/-) diaphragm expressed a low level of IL-1beta, IL-6, and IFN-gamma genes, a similar level of TNF-alpha, TGF-beta1, and platelet-derived growth factor alpha genes, and a high level of IGF-1 and osteopontin genes compared to mdx(5cv) controls. Diaphragm fibroblasts at 14 wk showed a similar cell number with a similar level of collagen and profibrogenic growth factor gene expression in mdx(5cv)-Ccr2(-/-) and mdx(5cv) mice. Diaphragm MPs from both mdx(5cv)-Ccr2(-/-) and mdx(5cv) mice stimulated collagen gene expression by cocultured fibroblasts. The findings suggest that CCR2 deficiency does not provide a sustained benefit and that Ly6C(low) MPs may contribute to the progressive fibrosis and dysfunction of mdx(5cv) diaphragm.-Zhao, W., Wang, X., Ransohoff, R. M., Zhou, L. CCR2 deficiency does not provide sustained improvement of muscular dystrophy in mdx(5cv) mice. |
