Department of Cardiology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China.
Department of Cardiology, Ezhou Central Hospital, Ezhou, Hubei 436000, P.R. China.
Mol Med Rep. 2023 Sep;28(3). doi: 10.3892/mmr.2023.13060. Epub 2023 Jul 28.
Tripartite motif‑containing 14 (TRIM14) is an E3 ubiquitin ligase that primarily participates in the natural immune response and in tumour development via ubiquitination. However, the role of TRIM14 in cardiac hypertrophy is not currently clear. The present study examined the role of TRIM14 in cardiac hypertrophy and its potential molecular mechanism. TRIM14 was overexpressed in neonatal rat cardiomyocytes using adenovirus and cardiomyocyte hypertrophy was induced using phenylephrine (PE). Cardiomyocyte hypertrophy was assessed by measuring cardiomyocyte surface area and markers of hypertrophy. In addition, TRIM14‑transgenic (TRIM14‑TG) mice were created and cardiac hypertrophy was induced using transverse aortic constriction (TAC). Cardiac function, heart weight‑to‑body weight ratio (HW/BW), cardiomyocyte cross‑sectional area, cardiac fibrosis and hypertrophic markers were further examined. The expression of AKT signalling pathway‑related proteins was detected. TRIM14 overexpression in cardiomyocytes promoted PE‑induced increases in cardiomyocyte surface area and hypertrophic markers. TRIM14‑TG mice developed worse cardiac function, greater HW/BW, cross‑sectional area and cardiac fibrosis, and higher levels of hypertrophic markers in response to TAC. TRIM14 overexpression also increased the phosphorylation levels of AKT, GSK‑3β, mTOR and p70S6K and . To the best our knowledge, the present study was the first to reveal that overexpression of TRIM14 aggravated cardiac hypertrophy and , which may be related to activation of the AKT signalling pathway.
三结构域蛋白 14（TRIM14）是一种 E3 泛素连接酶，主要通过泛素化参与天然免疫反应和肿瘤发生。然而，TRIM14 在心肌肥厚中的作用尚不清楚。本研究探讨了 TRIM14 在心肌肥厚中的作用及其潜在的分子机制。通过腺病毒过表达新生大鼠心肌细胞中的 TRIM14，并使用苯肾上腺素（PE）诱导心肌细胞肥大。通过测量心肌细胞表面积和肥大标志物来评估心肌细胞肥大。此外，还创建了 TRIM14 转基因（TRIM14-TG）小鼠，并使用横主动脉缩窄（TAC）诱导心肌肥厚。进一步检测了心脏功能、心脏重量与体重比（HW/BW）、心肌细胞横截面积、心肌纤维化和肥大标志物。检测 AKT 信号通路相关蛋白的表达。心肌细胞中 TRIM14 的过表达促进了 PE 诱导的心肌细胞表面积和肥大标志物的增加。TRIM14-TG 小鼠在 TAC 后表现出更差的心脏功能、更高的 HW/BW、更大的横截面积和更多的心肌纤维化以及更高水平的肥大标志物。TRIM14 的过表达还增加了 AKT、GSK-3β、mTOR 和 p70S6K 的磷酸化水平。据我们所知，本研究首次揭示了过表达 TRIM14 加重了心肌肥厚，这可能与 AKT 信号通路的激活有关。
