HIPK1, short for Homeodomain Interacting Protein Kinase 1, is a conserved serine/threonine kinase belonging to the CMGC superfamily. It can respond to different stress signals, interact with homeobox proteins and other transcription factors, and act as a transcriptional co-activator or corepressor. HIPK1 is involved in various biological processes such as signal transduction, apoptosis, and cellular proliferation [4].

In pathological cardiac hypertrophy, HIPK1 is increased. Both genetic ablation (KO) and gene therapy targeting HIPK1 protect against pathological hypertrophy and heart failure in vivo. HIPK1 inhibition prevents phenylephrine-induced cardiomyocyte hypertrophy by inhibiting CREB phosphorylation at Ser271 and inactivating C/EBPβ-mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy, suggesting HIPK1 as a potential therapeutic target for heart failure [1]. In acute lung injury (ALI), HIPK1 is elevated, and its interference by siRNA attenuates inflammation and oxidative stress indicators and enhances autophagy, indicating HIPK1 as a possible target in ALI management [3]. In adipocytes, lnc-hipk1 sponges miR-497, and overexpression of lnc-hipk1 inhibits adipocyte apoptosis by targeting the miR-497/Bcl-2 axis, which may provide new targets for treating obesity [2].

In conclusion, HIPK1 plays important roles in multiple biological processes and disease conditions. The use of gene knockout (KO) and other genetic models in mice has revealed its significance in pathological cardiac hypertrophy, acute lung injury, and adipocyte apoptosis. These findings suggest that HIPK1 could be a potential therapeutic target for related diseases.

References:

1. Bei, Yihua, Zhu, Yujiao, Wei, Meng, Sluijter, Joost Pg, Xiao, Junjie. 2023. HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPβ Axis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2300585. doi:10.1002/advs.202300585. https://pubmed.ncbi.nlm.nih.gov/37098980/

2. Wu, Qiong, Yang, Hong, Tai, Ruiqing, Liu, Yongnian, Sun, Chao. 2021. Lnc-hipk1 inhibits mouse adipocyte apoptosis as a sponge of miR-497. In BioFactors (Oxford, England), 48, 135-147. doi:10.1002/biof.1807. https://pubmed.ncbi.nlm.nih.gov/34856026/

3. Meng, Lan, Zhao, Xin, Zhang, Hongxia. 2019. HIPK1 Interference Attenuates Inflammation and Oxidative Stress of Acute Lung Injury via Autophagy. In Medical science monitor : international medical journal of experimental and clinical research, 25, 827-835. doi:10.12659/MSM.912507. https://pubmed.ncbi.nlm.nih.gov/30734722/

4. Conte, Andrea, Pierantoni, Giovanna Maria. . Update on the Regulation of HIPK1, HIPK2 and HIPK3 Protein Kinases by microRNAs. In MicroRNA (Shariqah, United Arab Emirates), 7, 178-186. doi:10.2174/2211536607666180525102330. https://pubmed.ncbi.nlm.nih.gov/29793420/