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

PeerJ. 2023 Aug 18:11:e15841. doi: 10.7717/peerj.15841. eCollection 2023.

Abstract

Background: 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.

Objectives: The purpose of this study was to describe the effects of TFEB on fibroblasts differentiation and extracellular matrix expression after MI.

Methods: 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.

Results: 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.

Conclusions: TFEB demonstrated potential in restraining fibrosis after MI by inhibiting the Wnt/β-catenin signaling pathway.

Keywords: Myocardial infarction; Transcription factor EB; Ventricular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics
  • Collagen Type I
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction* / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Remodeling*
  • Wnt Signaling Pathway
  • beta Catenin / genetics

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • beta Catenin
  • Collagen Type I
  • PNU-74654
  • TFEB protein, rat
  • Tcfeb protein, mouse

Grants and funding

XiaoXing Liao received support from the The National Science Fund for Distinguished Young Scholars (Grant Number: 81901931) and the Shenzhen Science and Technology Project (No. JCYJ20160608142215491). YuanZheng Lu received support from the Shenzhen Fundamental Research Program (jcyj20190809150817414) and the Guangdong Basic and Applied Basic Research Foundation (2020A15110827). HongYan Wei received support from the Basic and Applied Basic Research Fund of Guangdong Province (2020A1515010120). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.