Hmgb2, short for high-mobility group box 2, is a member of the high-mobility group chromosomal proteins, which are abundant nuclear non-histone proteins. HMGB2 is involved in a variety of biological processes such as cell differentiation, aging, and it can mediate the differentiation of embryonic and adult stem cells [2]. It also participates in multiple signaling pathways like RAGE/FAK-mediated Hippo/YAP signaling [1].

In disease-related studies, SMC-specific Hmgb2 knockout attenuated pulmonary hypertension development and pulmonary vascular remodeling in mouse models, indicating its role in promoting pulmonary hypertension [1]. In liver fibrosis, deletion of Hmgb2 in mice slowed the progression of carbon tetrachloride-induced liver fibrosis, suggesting Hmgb2 is crucial for hepatic stellate cell activation [3]. Hmgb2 deficiency also mitigated abdominal aortic aneurysm by suppressing Ang-II-caused ferroptosis and inflammation via the NF-κβ pathway in mice [4]. Moreover, Hmgb2-/-mice had a reduced incidence and mortality rate of aortic dissection, as Hmgb2 promotes smooth muscle cell proliferation in aortic dissection through the PPAR-γ/PGC-1α pathway-mediated glucose changes [5].

In conclusion, Hmgb2 is essential in multiple biological processes. Gene knockout mouse models have revealed its significance in diseases such as pulmonary hypertension, liver fibrosis, abdominal aortic aneurysm, and aortic dissection. These findings suggest that Hmgb2 could be a potential therapeutic target for these diseases, and further study of Hmgb2 may provide new insights into disease mechanisms and treatment strategies.