| First Author | Scheerer N | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 1 | Pages | 407-14 |
| PubMed ID | 23729446 | Mgi Jnum | J:205360 |
| Mgi Id | MGI:5544679 | Doi | 10.4049/jimmunol.1103779 |
| Citation | Scheerer N, et al. (2013) Myeloid hypoxia-inducible factor-1alpha is essential for skeletal muscle regeneration in mice. J Immunol 191(1):407-14 |
| abstractText | The outstanding regeneration ability of skeletal muscle is based on stem cells that become activated and develop to myoblasts after myotrauma. Proliferation and growth of myoblasts result in self-renewal of skeletal muscle. In this article, we show that myotrauma causes a hypoxic microenvironment leading to accumulation of the transcription factor hypoxia-inducible factor-1 (HIF-1) in skeletal muscle cells, as well as invading myeloid cells. To evaluate the impact of HIF-1 in skeletal muscle injury and repair, we examined mice with a conditional HIF-1alpha knockout targeted to skeletal muscle or myeloid cells in a model of soft tissue trauma. No differences in acute trauma size were detected between control and HIF-1alpha knockout mice. However, muscles of myeloid HIF-1alpha knockout mice showed a significant delay in myoblast proliferation and growth of regenerating myofibers, in association with decreased expression of cyclooxygenase-2 in HIF-1alpha-deficient myeloid cells. Moreover, the removal of necrotic cell debris and the regeneration of endothelial cell structure were impaired in myeloid HIF-1alpha knockout mice that showed delayed invasion of macrophages to the injury site. Our findings for the first time, to our knowledge, demonstrate that myeloid HIF-1alpha is required for adequate skeletal muscle regeneration. |
