In contrast to their role in promoting inflammation, the ability of alarmins to promote tissue repair and regeneration is of increasing interest (73) . Importantly, HMGB1 induces migration of stem cells toward inflamed regions to promote repair and regeneration (74) . Furthermore, it results in increased mesangioblast and endothelial proliferation and migration to sites of inflammation and induces transit of these cells across the endothelial layer (75, 76) . Myoblasts stimulated by HMGB1 migrate toward damaged regions and stimulate repair (77, 78) . These effects on specific cell types are reflected in increased regeneration at the tissue level. In smooth muscle, HMGB1 induces proliferation and rapid changes in cellular architec-ture leading to cell migration (79, 80) . In skeletal muscle, HMGB1 promotes increased myogenesis and angiogenesis (49, 76, 77) . Further confirmation of this is reflected in the finding that inhibition of HMGB1 signaling leads to decreased vessel density and tissue regeneration (77) . Additionally, direct injection of exogenous HMGB1 to peri-infarcted cardiomyocytes in mice results in increased myocytes within the infarcted area and ultimately improved outcomes by both structural and functional measures (81) . In an animal model of wound healing, topically applied HMGB1 accelerates the process in diabetic mice while inhibition of HMGB1 signaling slows it in normal mice, thus implicating functional HMGB1 signaling as an important component of diabetic wound healing (82) . The ability of HMGB1 to stimulate angiogenesis has been demonstrated independently in studies demonstrating that exogenous HMGB1 stimulates endothelial proliferation and migration (75, 83) . Interestingly, many of these restorative effects are mediated through the same receptors (i.e. RAGE) that mediate the pro-inflammatory properties of the molecule (75, (77) (78) (79) 84) . Taken together, the regenerative properties of HMGB1 represent a potentially important manner by which the functions of an alarmin can be manipulated to promote healing as opposed to injury.