Myeloid hypoxia-inducible factor-1? is essential for skeletal muscle regeneration in mice.

ABSTRACT: 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-1? 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-1? knockout mice. However, muscles of myeloid HIF-1? knockout mice showed a significant delay in myoblast proliferation and growth of regenerating myofibers, in association with decreased expression of cyclooxygenase-2 in HIF-1?-deficient myeloid cells. Moreover, the removal of necrotic cell debris and the regeneration of endothelial cell structure were impaired in myeloid HIF-1? 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-1? is required for adequate skeletal muscle regeneration.

SUBMITTER: Scheerer N 

PROVIDER: S-EPMC6614040 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature