Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy

Ya Fang Chen, Nien Hung Lee, Pei Ying Pai, Li Chin Chung, Chia Yao Shen, Peramaiyan Rajendran, Yu Feng Chen, Ray Jade Chen, Vijaya Padma Viswanadha, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Cardiomyopathy involves changes in myocardial ultrastructure and cardiac hypertrophy. Angiotensin II (AngII) has previously been shown to stimulate the expression of IGF-2 and IGF-2R in H9c2 cardiomyoblasts and increase of blood pressure, and cardiac hypertrophy. Estrogen receptors (ERs) exert protective effects, such as anti-hypertrophy in cadiomyocytes. Tanshinone IIA (TSN), a main active ingredient from a Chinese medical herb, Salvia miltiorrhiza Bunge (Danshen), was shown to protect cardiomyocytes hypertrophy by different stress signals. We aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy by mediating through ERs. AngII resulted in H9c2 cardiomyoblast hypertrophy and increased inflammatory molecular markers. These were down-regulated by TSN via estrogen receptors. AngII resulted in elevation in MAPKs, IGF-2R and hypertrophic protein markers. These, again, were reduced by addition of the phytoestrogen with activation of ERs. Finally, AngII induced phosphorylation of heat shock factor-1 (HSF1) and decreased sirtuin-1 (SIRT1). In addition, AngII also caused an increase in distribution of IGF-2R molecules on cell membrane. In contrast, TSN reduced HSF1 phosphorylation and cell surface IGF-2R while elevating SIRT1 via ERs. TSN was capable of attenuating AngII-induced IGF-2R pathway and hypertrophy through ERs in H9c2 cardiomyoblast cells.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalJournal of Receptors and Signal Transduction
Issue number5
Publication statusPublished - Sept 3 2017


  • Angiotensin II
  • H9c2 cardiomyoblasts
  • IGF-2R
  • estrogen receptors
  • hypertrophy
  • tanshinone IIA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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