Hmgb2, or 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, interacting with DNA and protein partners, and has roles in cell differentiation, aging, and stem cell differentiation [2].

In disease-related studies, SMC-specific Hmgb2 knockout attenuated pulmonary hypertension (PH) development and pulmonary vascular remodeling in hypoxia + Su5416-induced mice, suggesting Hmgb2 promotes PH by RAGE/FAK-mediated Hippo/YAP signaling suppression [1]. In liver fibrosis, Hmgb2 deletion in mice slowed the progression of CCl4-induced liver fibrosis, indicating Hmgb2 is indispensable for stellate cell activation [3]. In abdominal aortic aneurysm (AAA), Hmgb2 depletion mitigated AAA by suppressing Ang-II-caused ferroptosis and inflammation via the NF-κβ pathway [4]. In aortic dissection (AD), Hmgb2-/-mice had reduced incidence and mortality rates of AD, as Hmgb2 promotes smooth muscle cell proliferation through the PPAR-γ/PGC-1α pathway-mediated glucose changes [5].

In conclusion, Hmgb2 plays essential roles in multiple biological processes and disease conditions. Gene-knockout mouse models, such as in PH, liver fibrosis, AAA, and AD, have been crucial in revealing its functions. These studies suggest Hmgb2 could be a potential therapeutic target in these disease areas.

References:

1. Kong, Deping, Liu, Jing, Lu, Junmi, Li, Jiang, He, Yuhu. 2024. HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension. In Arteriosclerosis, thrombosis, and vascular biology, 44, e172-e195. doi:10.1161/ATVBAHA.123.319916. https://pubmed.ncbi.nlm.nih.gov/38572649/

2. Starkova, Tatiana, Polyanichko, Alexander, Tomilin, Alexey N, Chikhirzhina, Elena. 2023. Structure and Functions of HMGB2 Protein. In International journal of molecular sciences, 24, . doi:10.3390/ijms24098334. https://pubmed.ncbi.nlm.nih.gov/37176041/

3. Huang, Yi, Liangpunsakul, Suthat, Rudraiah, Swetha, Wang, Li, Yang, Zhihong. 2023. HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis. In Hepatology communications, 7, . doi:10.1097/HC9.0000000000000299. https://pubmed.ncbi.nlm.nih.gov/37930124/

4. Wu, Hao, Chen, Legao, Lu, Kaiping, Jiang, Jinsong, Weng, Chao. 2023. HMGB2 Deficiency Mitigates Abdominal Aortic Aneurysm by Suppressing Ang-II-Caused Ferroptosis and Inflammation via NF-κβ Pathway. In Mediators of inflammation, 2023, 2157355. doi:10.1155/2023/2157355. https://pubmed.ncbi.nlm.nih.gov/38148870/

5. Zheng, Yameng, Yao, Mengge, Chen, Shaokun, Chen, Liangwan, Zhang, Li. 2024. HMGB2 promotes smooth muscle cell proliferation through PPAR-γ/PGC-1α pathway-mediated glucose changes in aortic dissection. In Atherosclerosis, 399, 119044. doi:10.1016/j.atherosclerosis.2024.119044. https://pubmed.ncbi.nlm.nih.gov/39531897/