Effects of Transient Hypoxia versus Prolonged Hypoxia on Satellite Cell Proliferation and Differentiation In Vivo

Stem Cells International
Sukanta Jash, Samit Adhya

Abstract

The microenvironment of the injury site can have profound effects on wound healing. Muscle injury results in ischemia leading to short-term local hypoxia, but there are conflicting reports on the role of hypoxia on the myogenic program in vivo and in vitro. In our rat model of mitochondrial restoration (MR), temporary upregulation of mitochondrial activity by a cocktail of organelle-encoded RNAs results in satellite cell proliferation and initiation of myogenesis. We now report that MR leads to a transient hypoxic response in situ. Inhibition of hypoxia by lowering mitochondrial O2 consumption, either by respiratory electron transport inhibitors, or by NO-mediated inhibition of O2 binding to cytochrome c oxidase, resulted in exacerbation of inflammation. Lentivirus-mediated knockdown of hypoxia-inducible factor 1α (HIF1α) or of Notch signaling components had a similar effect, and pharmacologic inhibition of HIF or Notch reduced the number of proliferating Pax7(+) cells. In contrast, a prolonged hypoxic response induced either by uncoupling of respiration from oxidative phosphorylation or through HIF stabilization by dimethyloxalylglycine (DMOG) had an immediate anti-inflammatory effect. Although significant satellite cell proli...Continue Reading

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Citations

Oct 11, 2016·Oxidative Medicine and Cellular Longevity·Hiroshi NagahisaHirofumi Miyata
Apr 11, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Krishna M SinhaJohnny Huard
Sep 8, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas Chaillou, Johanna T Lanner
Nov 16, 2016·Molecular and Cellular Biochemistry·Deepthi Sreerengam RajendranNairRenuka R Nair

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Methods Mentioned

BETA
confocal microscopy
PCR
transfection

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