TY - JOUR
T1 - Hypoxia-inducible factor 1α (HIF-1α) is a major determinant in the enhanced function of muscle-derived progenitors from MRL/MpJ mice
AU - Sinha, Krishna M.
AU - Tseng, Chieh
AU - Guo, Ping
AU - Lu, Aiping
AU - Pan, Haiying
AU - Gao, Xueqin
AU - Andrews, Reid
AU - Eltzschig, Holger
AU - Huard, Johnny
N1 - Publisher Copyright:
© FASEB
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Although the mouse strain Murphy Roths Large (MRL/MpJ) possesses high regenerative potential, the mechanism of tissue regeneration, including skeletal muscle, in MRL/MpJ mice after injury is still unclear. Our previous studies have shown that muscle-derived stem/progenitor cell (MDSPC) function is significantly enhanced in MRL/MpJ mice when compared with MDSPCs isolated from age-matched wild-type (WT) mice. Using mass spectrometry–based proteomic analysis, we identified increased expression of hypoxia-inducible factor (HIF) 1α target genes (expression of glycolytic factors and antioxidants) in sera from MRL/MpJ mice compared with WT mice. Therefore, we hypothesized that HIF-1α promotes the high muscle healing capacity of MRL/MpJ mice by increasing the potency of MDSPCs. We demonstrated that treating MRL/MpJ MDSPCs with dimethyloxalylglycine and CoCl2 increased the expression of HIF-1α and target genes, including angiogenic and cell survival genes. We also observed that HIF-1α activated the expression of paired box (Pax)7 through direct interaction with the Pax7 promoter. Furthermore, we also observed a higher myogenic potential of MDSPCs derived from prolyl hydroxylase (Phd) 3—knockout (Phd3−/−) mice, which displayed higher stability of HIF-1α. Taken together, our findings suggest that HIF-1α is a major determinant in the increased MDSPC function of MRL/MpJ mice through enhancement of cell survival, proliferation, and myogenic differentiation.—Sinha, K. M., Tseng, C., Guo, P., Lu, A., Pan, H., Gao, X., Andrews, R., Eltzschig, H., Huard, J. Hypoxia-inducible factor 1α (HIF-1α) is a major determinant in the enhanced function of muscle-derived progenitors from MRL/MpJ mice. FASEB J. 33, 8321–8334 (2019). www.fasebj.org.
AB - Although the mouse strain Murphy Roths Large (MRL/MpJ) possesses high regenerative potential, the mechanism of tissue regeneration, including skeletal muscle, in MRL/MpJ mice after injury is still unclear. Our previous studies have shown that muscle-derived stem/progenitor cell (MDSPC) function is significantly enhanced in MRL/MpJ mice when compared with MDSPCs isolated from age-matched wild-type (WT) mice. Using mass spectrometry–based proteomic analysis, we identified increased expression of hypoxia-inducible factor (HIF) 1α target genes (expression of glycolytic factors and antioxidants) in sera from MRL/MpJ mice compared with WT mice. Therefore, we hypothesized that HIF-1α promotes the high muscle healing capacity of MRL/MpJ mice by increasing the potency of MDSPCs. We demonstrated that treating MRL/MpJ MDSPCs with dimethyloxalylglycine and CoCl2 increased the expression of HIF-1α and target genes, including angiogenic and cell survival genes. We also observed that HIF-1α activated the expression of paired box (Pax)7 through direct interaction with the Pax7 promoter. Furthermore, we also observed a higher myogenic potential of MDSPCs derived from prolyl hydroxylase (Phd) 3—knockout (Phd3−/−) mice, which displayed higher stability of HIF-1α. Taken together, our findings suggest that HIF-1α is a major determinant in the increased MDSPC function of MRL/MpJ mice through enhancement of cell survival, proliferation, and myogenic differentiation.—Sinha, K. M., Tseng, C., Guo, P., Lu, A., Pan, H., Gao, X., Andrews, R., Eltzschig, H., Huard, J. Hypoxia-inducible factor 1α (HIF-1α) is a major determinant in the enhanced function of muscle-derived progenitors from MRL/MpJ mice. FASEB J. 33, 8321–8334 (2019). www.fasebj.org.
KW - muscle progenitor cells
KW - myogenic differentiation
KW - stem cell potency
KW - tissue regeneration
UR - http://www.scopus.com/inward/record.url?scp=85069234393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069234393&partnerID=8YFLogxK
U2 - 10.1096/fj.201801794R
DO - 10.1096/fj.201801794R
M3 - Article
C2 - 30970214
AN - SCOPUS:85069234393
SN - 0892-6638
VL - 33
SP - 8321
EP - 8334
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -