HspB2, also known as Myotonic Dystrophy Kinase Binding Protein (MKBP), is a member of the small heat-shock protein family. Small heat-shock proteins are involved in maintaining proteome functionality and stability, acting as molecular chaperones to suppress protein aggregation. HspB2 has been implicated in multiple biological processes and disease-related pathways.

In a cardiac-specific HspB2 deficient (HSPB2cKO) mouse model, HSPB2 was dispensable for the cardiac hypertrophic response under basal conditions. However, following pressure overload, the absence of HSPB2 led to reduced mitochondrial energetics, with changes in the transcript levels of several metabolic and mitochondrial regulator genes, suggesting its role in regulating metabolic/mitochondrial function during cardiac stress. In another study, knockout of αB-crystallin/HspB2 in a mouse model with cardiac Tsc1 deletion reversed deficient Tsc1-mediated fetal gene expression, mTOR activation, mitochondrial damage, and other pathological changes, improving cardiac function and reducing lethality, indicating their pivotal role in Tsc1 knockout-related cardiomyopathy.

In conclusion, HspB2 plays a role in maintaining proteome stability as a molecular chaperone. Mouse models, especially KO/CKO models, have revealed its importance in cardiac-related diseases, such as Tsc1 knockout-related cardiomyopathy and in regulating mitochondrial function during cardiac stress. These findings provide insights into potential therapeutic targets for related cardiac pathologies.

References:

1. Wang, Lianmei, Wang, Fang, Liu, Kemei, Yan, Hongbing, Zhang, Hongbing. 2021. αB-crystallin/HSPB2 is critical for hyperactive mTOR-induced cardiomyopathy. In Journal of cellular physiology, 236, 8110-8121. doi:10.1002/jcp.30465. https://pubmed.ncbi.nlm.nih.gov/34101831/

2. Hu, Zhiping, Yang, Binbin, Lu, Wei, Li, Ting, Wang, Xiang. . HSPB2/MKBP, a novel and unique member of the small heat-shock protein family. In Journal of neuroscience research, 86, 2125-33. doi:10.1002/jnr.21682. https://pubmed.ncbi.nlm.nih.gov/18615620/

3. Ishiwata, Takahiro, Orosz, András, Wang, Xiaohui, Abel, E Dale, Benjamin, Ivor J. 2012. HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice. In PloS one, 7, e42118. doi:10.1371/journal.pone.0042118. https://pubmed.ncbi.nlm.nih.gov/22870288/