AUTHOR=Gupta Naveen , Nizet Victor TITLE=Stabilization of Hypoxia-Inducible Factor-1 Alpha Augments the Therapeutic Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Pneumonia JOURNAL=Frontiers in Medicine VOLUME=5 YEAR=2018 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2018.00131 DOI=10.3389/fmed.2018.00131 ISSN=2296-858X ABSTRACT=
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc.), which blocks the pathway for HIF-1α degradation in the proteosome.