PT  - JOURNAL ARTICLE
AU  - Xing-Hua Liao
AU  - Yuan Xiang
AU  - Jia-Peng Li
AU  - Hui Li
AU  - You Huang
AU  - Chao Shen
AU  - Hui-Min Zhang
AU  - Tong-Cun Zhang
TI  - STAT3 inhibits Myocardin induced cardiac hypertrophy
AID  - 10.1101/2020.11.21.392902
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.21.392902
4099  - http://biorxiv.org/content/early/2020/11/22/2020.11.21.392902.short
4100  - http://biorxiv.org/content/early/2020/11/22/2020.11.21.392902.full
AB  - Background In order to explore the molecular mechanism of cardiomyocyte-dependent myocardial gene expression and cardiomyocyte differentiation in cardiac hypertrophy, and to provide new insights for cardiac hypertrophy.Methods Cardiac myocytes were isolated from day 1-3 Sprague-Dawley rat pups. Real time quantitative PCR, western blot and immunocytochemistry Assay were used to detect the expression and localization of related genes. CO-IP was used to detect direct protein interactions between Myocardin and STAT3. Luciferase reporter assay and chromatin immunoprecipitation were used to detect the binding of Myocardin to the promoter of a downstream target gene. Microinjection of zebrafish embryos was used to examine the effects of STAT3 and Myocardin interactions on cardiac development in vivoResults The N-terminus of STAT3 directly binds to the basic domain of myocardin and inhibits the transcriptional activity of Myocardin-mediated cardiac-specific genes ANF and α-actinin, thereby inhibiting their expression, and further inhibit myocardin-mediated cardiac hypertrophy in vivo.Conclusions In summary, our report states that signal transduction and transcriptional activation factor 3 (STAT3) are inhibitors of the major cardiac hypertrophic transcription factor Myocardiin, which is required for cardiomyocyte differentiation. The STAT3-cardiacin interaction identified nuclear hormone receptor-mediated and cardiac-specific gene-regulated convergence sites and suggested a possible mechanism for cardioprotective effects.AbbreviationsSTAT3signal transducer and activator of transcription 3;SRFserum response factor;IL-6interleukin-6;LIFleukemia inhibitory factor;DMEMDulbecco’s modified Eagle’s medium;DAPI4’,6’-diamidino-2-phenylindole;RT-PCRsemi-quantitative reverse-transcription polymerase chain reaction;qPCRreal time quantitative polymerase chain reaction;GAPDHGlyceraldehyde-3-phosphate dehydrogenase;PAGEsodium dodecyl sulfate-polyacrylamide gel electrophoresis;ChIPChromatin Immunoprecipitation;JAKJanus kinase;LPSlipopolysaccharide;ERK1/2extracellular regulated protein kinases;PIAS1protein inhibitor of activated STAT 1;SUMO1small uniquitin-like modifier 1;MOMorpholino