β-catenin/LEF1/IGF-IIR Signaling Axis Galvanizes the Angiotensin-II-induced Cardiac Hypertrophy

Chin Hu Lai, Sudhir Pandey, Cecilia Hsuan Day, Tsung Jung Ho, Ray Jade Chen, Ruey Lin Chang, Pei Ying Pai, V. Vijaya Padma, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticle

Abstract

Cardiovascular diseases have a high prevalence worldwide and constitute the leading causes of mortality. Recently, malfunctioning of β-catenin signaling has been addressed in hypertensive heart condition. Ang-II is an important mediator of cardiovascular remodeling processes which not only regulates blood pressure but also leads to pathological cardiac changes. However, the contribution of Ang-II/β-catenin axis in hypertrophied hearts is ill-defined. Employing in vitro H9c2 cells and in vivo spontaneously hypertensive rats (SHR) cardiac tissue samples, western blot analysis, luciferase assays, nuclear-cytosolic protein extracts, and immunoprecipitation assays, we found that under hypertensive condition β-catenin gets abnormally induced that co-activated LEF1 and lead to cardiac hypertrophy changes by up-regulating the IGF-IIR signaling pathway. We identified putative LEF1 consensus binding site on IGF-IIR promoter that could be regulated by β-catenin/LEF1 which in turn modulate the expression of cardiac hypertrophy agents. This study suggested that suppression of β-catenin expression under hypertensive condition could be exploited as a clinical strategy for cardiac pathological remodeling processes.

Original languageEnglish
Article number4288
JournalInternational Journal of Molecular Sciences
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2019

Keywords

  • Ang-II
  • IGF-IIR
  • LEF1
  • β-catenin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Lai, C. H., Pandey, S., Day, C. H., Ho, T. J., Chen, R. J., Chang, R. L., Pai, P. Y., Padma, V. V., Kuo, W. W., & Huang, C. Y. (2019). β-catenin/LEF1/IGF-IIR Signaling Axis Galvanizes the Angiotensin-II-induced Cardiac Hypertrophy. International Journal of Molecular Sciences, 20(17), [4288]. https://doi.org/10.3390/ijms20174288