Hspa12b, a member of the HSP70 protein family, is predominantly expressed in endothelial cells. It plays essential roles in angiogenesis, inflammation regulation, and tissue repair. It is involved in multiple pathways such as the PI3K/Akt signaling pathway. Genetic models, like KO or CKO mouse models, are valuable for studying its functions [1,2,3,4,5].

In gene-related functional studies, endothelial-specific knockout of Hspa12b (eHspa12b-/-) in a myocardial infarction (MI) mouse model impaired angiogenesis and exacerbated cardiac dysfunction compared with WT mice, indicating its importance in post-MI angiogenesis [1]. In a sepsis mouse model, Hspa12b knockout (HSPA12B-/-) accelerated mortality and caused severe cardiac dysfunction, along with increased adhesion molecules and immune cell infiltration in the myocardium, suggesting its protective role against sepsis-induced cardiomyopathy [3].

In conclusion, Hspa12b is crucial for angiogenesis, protecting against tissue injuries like acute lung injury, sepsis-induced cardiomyopathy, and myocardial ischemia/reperfusion injury. The use of Hspa12b KO/CKO mouse models has significantly contributed to understanding its role in these disease areas, providing insights for potential therapeutic strategies targeting these conditions [1,2,3,5].

References:

1. Fan, Min, Yang, Kun, Wang, Xiaohui, Williams, David L, Li, Chuanfu. 2020. Endothelial cell HSPA12B and yes-associated protein cooperatively regulate angiogenesis following myocardial infarction. In JCI insight, 5, . doi:10.1172/jci.insight.139640. https://pubmed.ncbi.nlm.nih.gov/32790647/

2. Zhang, Xiaojin, Li, Jingjin, Li, Chuanfu, Ding, Zhengnian, Liu, Li. 2015. HSPA12B attenuates acute lung injury during endotoxemia in mice. In International immunopharmacology, 29, 599-606. doi:10.1016/j.intimp.2015.09.022. https://pubmed.ncbi.nlm.nih.gov/26428851/

3. Zhang, Xia, Wang, Xiaohui, Fan, Min, Williams, David, Li, Chuanfu. 2020. Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126. In Frontiers in immunology, 11, 566. doi:10.3389/fimmu.2020.00566. https://pubmed.ncbi.nlm.nih.gov/32411123/

4. Wu, Jun, Li, Xuehan, Huang, Lei, Ding, Zhengnian, Liu, Li. 2014. HSPA12B inhibits lipopolysaccharide-induced inflammatory response in human umbilical vein endothelial cells. In Journal of cellular and molecular medicine, 19, 544-54. doi:10.1111/jcmm.12464. https://pubmed.ncbi.nlm.nih.gov/25545050/

5. Kong, Qiuyue, Dai, Leyang, Wang, Yana, Ding, Zhengnian, Liu, Li. 2016. HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism. In Scientific reports, 6, 33636. doi:10.1038/srep33636. https://pubmed.ncbi.nlm.nih.gov/27644317/