Hypoxia and Hypoxia Signaling in Tissue Repair and Fibrosis

The role of iNOS in cholesterol-induced liver fibrosis

“…Indeed, many genes under the regulation of HIF-1 have been implicated in the pathogenesis of liver fibrosis as well as in ECM modifications. [43][44][45][46][47][48][49] HIF-1-deficient mice develop less liver Cholesterol, iNOS, and liver fibrosis S Anavi et al fibrosis following bile duct ligation. 46 Moon et al 46 demonstrated reduced expression of several profibrotic mediators and reduced production of collagenous matrix in HIF-1 liverdeficient mice.…”

Integrins in Wound Healing

“…8 Additional activating signals include the disruption of cell-cell connections, changes in oxygen tension, exposure to new ECM molecules, and changes in mechanical tension in the tissue itself. 8,[120][121][122] In addition, the circulating fibroblast-like cells (fibrocytes) may serve as important precursor cells to pericytes in wound healing. 123 Connective tissue cell activation extends far from the wound edge, as evidenced by localization of the induction of fibroblast activating protein (FAP or seprase) expression at cells distant from the wound edge.…”

N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs

“…Regardless of the origins of the hypoxic stress, cells must alter their metabolism and gene expression in ways that will increase their chance of survival, or succumb to apoptosis. The physiological response to hypoxia is initiated by the stabilization of the hypoxia-inducible factor-1α (HIF-1α) transcription factor targeting genes containing a hypoxia response element (HRE) (Wenger et al 2005;Lokmic et al 2012;Hong et al 2014;Semenza 2014b). HIF-1α is also important for promoting cancer cell survival through interactions with Myc and Jun, and it is well documented that hypoxia drives tumor angiogenesis (Harris 2002;Laderoute et al 2002;Nelson et al 2004;Dang et al 2008;Rankin and Giaccia 2008;Li et al 2009;Foster et al 2014).…”