文献类型：期刊文献

英文题名：TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy

作者：Han, Ziqi[1,2];Dong, Qianqian[2];Lu, Xiao[1,2];Liu, Shanshan[1,2];Yang, Yanlong[1,2];Shao, Feifei[2];Tian, Limin[1,3]

第一作者：Han, Ziqi

通信作者：Tian, LM[1];Tian, LM[2]

机构：[1]Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China;[2]Gansu Prov Hosp, Dept Endocrinol, Lanzhou 730000, Peoples R China;[3]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol, Chengdu 610000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China;[2]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Endocrinol, Chengdu 610000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

外文期刊名：JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION

收录：;Scopus(收录号：2-s2.0-86000648327);WOS:【SCI-EXPANDED(收录号:WOS:001439522600001)】；

基金：This work was supported by the National Natural Science Foundation of China (82060152) and the Natural Science Foundation of Gansu Province (22JR5RA648).

语种：英文

外文关键词：TSH; Cardiac hypertrophy; Subclinical Hypothyroidism; CYP450 enzyme

摘要：BackgroundSubclinical hypothyroidism (SCH) is closely associated with heart failure and cardiac hypertrophy, yet the underlying mechanism remains unclear.MethodsCardiomyocytes treated with thyroid-stimulating hormone (TSH) were used as an in vitro model. Cardiac-specific TSHR knockout mice (CKO) were treated with isoproterenol (ISO) to induce cardiac hypertrophy in vivo. Serum FT4, TSH levels, heart weight, body weight and tibial length of mice were evaluated. Heart function was analyzed by M-mode cardiac ultrasonography. The pathological changes in cardiac tissues were detected by immunohistochemistry, hematoxylin-eosin and WGA staining. mRNA levels of ANP, BNP, alpha-MHC and beta-MHC were evaluated by RT-PCR. Western blot was used to detect pathway related proteins. Besides, the transcriptome sequencing analysis and dual-luciferase reporter assays were used to verify the relevant molecular mechanisms.ResultsTSH significantly promotes cardiomyocyte hypertrophy in cardiomyocytes. Meanwhile, cardiac-specific TSHR knockout significantly reduced ISO-induced cardiac hypertrophy. This was demonstrated by reductions in cell sizes, decreased HW/BW and HW/TL ratios, along with improved expression of hypertrophic genes. Further transcriptome sequencing results showed that TSH can significantly promote the expression of CYP4B1 in vitro. And the knockdown of CYP4B1 repressed TSH-induced cardiomyocyte hypertrophy. Further mechanistic studies revealed that TSH regulated the expression of CYP4B1 hypertrophy through the PI3K/AKT/CREB signaling pathway. Subsequently, the dual-luciferase assays demonstrated that CREB promotes the transcription of CYP4B1 by binding to its promoter region.ConclusionOverall, our findings highlight the direct impact of TSH/TSHR on cardiomyocyte hypertrophy and proposed CYP4B1 as a promising target for mitigating cardiac hypertrophy in SCH patients.