Shu Jin, Shi Jue, Gu Yiwen, Deng Lei, Zhao Chen, Wu Chun, Zhao Jiachen, Wang Haiya, Jin Li
Department of Gerontology, Shibei Hospital of Jing'an District, Shanghai, 200443, China.
Department of Gerontology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200023, China.
Open Life Sci. 2023 Feb 9;18(1):20220554. doi: 10.1515/biol-2022-0554. eCollection 2023.
This study aimed to explore the effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP-1-OE plasmid/si‑TIMP-1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated , , and expression ( < 0.05) and downregulated and expression ( < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis ( < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated , and expression caused by AngII and upregulated caspase 3, p53, and expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression.
本研究旨在探讨金属蛋白酶组织抑制剂-1（TIMP-1）对左旋肉碱（LC）介导的血管紧张素II（AngII）诱导的心肌纤维化（MF）调节作用及其潜在机制。用AngII处理H9C2细胞24小时以诱导纤维化。然后用LC处理细胞或用TIMP-1过表达质粒/小干扰RNA（si-TIMP-1）转染细胞。分析细胞凋亡、活力、迁移及相关基因表达。与对照水平相比，AngII处理显著上调了 、 和 的表达（ < 0.05），并下调了 和 的表达（ < 0.05）。转染后，成功建立了TIMP-1过表达/敲低的细胞。与对照相比，AngII显著抑制细胞活力和细胞迁移，同时促进细胞凋亡（ < 0.05）。LC和TIMP-1过表达转染进一步抑制了Ang II诱导的细胞活力和迁移，并上调了细胞凋亡，而si-TIMP-1则产生相反的效果。此外，LC和TIMP-1过表达转染下调了AngII引起的 、 和 的表达，并上调了半胱天冬酶3、p53和 的表达，而si-TIMP-1则产生相反的效果。因此，TIMP-1是延缓MF进展的潜在治疗靶点。
