| First Author | Kozakowska M | Year | 2018 |
| Journal | Am J Pathol | Volume | 188 |
| Issue | 2 | Pages | 491-506 |
| PubMed ID | 29169990 | Mgi Jnum | J:258257 |
| Mgi Id | MGI:6117950 | Doi | 10.1016/j.ajpath.2017.10.017 |
| Citation | Kozakowska M, et al. (2018) Lack of Heme Oxygenase-1 Induces Inflammatory Reaction and Proliferation of Muscle Satellite Cells after Cardiotoxin-Induced Skeletal Muscle Injury. Am J Pathol 188(2):491-506 |
| abstractText | Heme oxygenase-1 (HO-1, Hmox1) regulates viability, proliferation, and differentiation of many cell types; hence, it may affect regeneration of injured skeletal muscle. Here, we injected cardiotoxin into gastrocnemius muscle of Hmox1(+/+) and Hmox1(-/-) animals and analyzed cellular response after muscle injury, focusing on muscle satellite cells (SCs), inflammatory reaction, fibrosis, and formation of new blood vessels. HO-1 is strongly induced after muscle injury, being expressed mostly in the infiltrating leukocytes (CD45(+) cells), including macrophages (F4/80(+) cells). Lack of HO-1 augments skeletal muscle injury, evidenced by increased creatinine kinase and lactate dehydrogenase, as well as expression of monocyte chemoattractant protein-1, IL-6, IL-1beta, and insulin-like growth factor-1. This, together with disturbed proportion of M1/M2 macrophages, accompanied by enhanced formation of arterioles, may be responsible for shift of Hmox1(-/-) myofiber size distribution toward larger one. Importantly, HO-1-deficient SCs are prone to activation and have higher proliferation on injury. This effect can be partially mimicked by stimulation of Hmox1(+/+) SCs with monocyte chemoattractant protein-1, IL-6, IL-1beta, and is associated with increased MyoD expression, suggesting that Hmox1(-/-) SCs are shifted toward more differentiated myogenic population. However, multiple rounds of degeneration/regeneration in conditions of HO-1 deficiency may lead to exhaustion of SC pool, and the number of SCs is decreased in old Hmox1(-/-) mice. In summary, HO-1 modulates muscle repair mechanisms preventing its uncontrolled acceleration. |
