@article{4962fc4c8d8f4010baf39def7ad6ed1e,
title = "HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPβ Axis",
abstract = "Inhibition of pathological cardiac hypertrophy is recognized as an important therapeutic strategy for heart failure, although effective targets are still lacking in clinical practice. Homeodomain interacting protein kinase 1 (HIPK1) is a conserved serine/threonine kinase that can respond to different stress signals, however, whether and how HIPK1 regulates myocardial function is not reported. Here, it is observed that HIPK1 is increased during pathological cardiac hypertrophy. Both genetic ablation and gene therapy targeting HIPK1 are protective against pathological hypertrophy and heart failure in vivo. Hypertrophic stress-induced HIPK1 is present in the nucleus of cardiomyocytes, while HIPK1 inhibition prevents phenylephrine-induced cardiomyocyte hypertrophy through inhibiting cAMP-response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer-binding protein β (C/EBPβ)-mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy. In conclusion, HIPK1 inhibition may serve as a promising novel therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.",
keywords = "C/EBPβ, cardiomyocytes, CREB, HIPK1, pathological hypertrophy",
author = "Yihua Bei and Yujiao Zhu and Meng Wei and Mingming Yin and Lin Li and Chen Chen and Zhenzhen Huang and Xuchun Liang and Juan Gao and Jianhua Yao and {van der Kraak}, {Petra H} and Aryan Vink and Zhiyong Lei and Yuxiang Dai and Huihua Chen and Yueyang Liang and Sluijter, {Joost Pg} and Junjie Xiao",
note = "Funding Information: This work was supported by the grants from National Key Research and Development Project (2020YFA0803800 to Y.H.B.), National Natural Science Foundation of China (82020108002 and 82225005 to J.J.X., 81970335 and 82170285 to Y.H.B.), the grant from Science and Technology Commission of Shanghai Municipality (21XD1421300 and 20DZ2255400 to J.J.X., 23010500300 and 21SQBS00100 to Y.H.B.), the “Dawn” Program of Shanghai Education Commission (19SG34 to J.J.X.), Shanghai Rising-Star Program (19QA1403900 to Y.H.B.), Natural Science Foundation of Shanghai (20ZR1443300 to J.H.Y.), Natural Science Foundation of Tibet Autonomous Region (XZ2020ZR-ZY35(Z) and XZ202101ZR0003G to J.H.Y.). J.S. is supported by Horizon2020 ERC-2016-COG EVICARE (725229). Funding Information: This work was supported by the grants from National Key Research and Development Project (2020YFA0803800 to Y.H.B.), National Natural Science Foundation of China (82020108002 and 82225005 to J.J.X., 81970335 and 82170285 to Y.H.B.), the grant from Science and Technology Commission of Shanghai Municipality (21XD1421300 and 20DZ2255400 to J.J.X., 23010500300 and 21SQBS00100 to Y.H.B.), the “Dawn” Program of Shanghai Education Commission (19SG34 to J.J.X.), Shanghai Rising‐Star Program (19QA1403900 to Y.H.B.), Natural Science Foundation of Shanghai (20ZR1443300 to J.H.Y.), Natural Science Foundation of Tibet Autonomous Region (XZ2020ZR‐ZY35(Z) and XZ202101ZR0003G to J.H.Y.). J.S. is supported by Horizon2020 ERC‐2016‐COG EVICARE (725229). Publisher Copyright: {\textcopyright} 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.",
year = "2023",
month = jun,
doi = "10.1002/advs.202300585",
language = "English",
volume = "10",
journal = "Advanced Science",
publisher = "Wiley-VCH Verlag",
number = "18",
}