Transcription factor EB (TFEB) improves ventricular remodeling after myocardial infarction by inhibiting Wnt/β-catenin signaling pathway.

Cong Liu, Dawang Zhou, Qiang Zhang, Hongyan Wei, Yuanzheng Lu, Bo Li, Haohong Zhan, Jingge Cheng, Chuyue Wang, Yilin Yang, Shuhao Li, Chunlin Hu, Xiaoxing Liao

PeerJ 2023

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Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Until now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited. The purpose of this study was to describe the effects of TFEB on fibroblasts differentiation and extracellular matrix expression after MI. AAV9 (adeno-associated virus) mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), immunofluorescence, wound healing and Transwell assay were conducted. Myocardial fibrosis-related proteins were identified by Western blot. PNU-74654 (100 ng/mL) was used for 12 hours to inhibit β-catenin-TCF/LEF1 complex. The up-regulation of TFEB resulted in reduced fibroblasts proliferation and its differentiation into myofibroblasts in vitro studies. A significant up-regulation of EF and down-regulation of myocyte area was shown in the AAV9-TFEB group. Meanwhile, decreased protein level of α-SMA and collagen I were observed in vitro study. TFEB didn't affect the concentration of β-catenin. Inhibition of TFEB, which promoted cell migration, proliferation and collagen I expression, was counteracted by PNU-74654. TFEB demonstrated potential in restraining fibrosis after MI by inhibiting the Wnt/β-catenin signaling pathway. ©2023 Liu et al.

Citation

Cong Liu, Dawang Zhou, Qiang Zhang, Hongyan Wei, Yuanzheng Lu, Bo Li, Haohong Zhan, Jingge Cheng, Chuyue Wang, Yilin Yang, Shuhao Li, Chunlin Hu, Xiaoxing Liao. Transcription factor EB (TFEB) improves ventricular remodeling after myocardial infarction by inhibiting Wnt/β-catenin signaling pathway. PeerJ. 2023;11:e15841