Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.
Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.
Department of Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing 100081, China.
Dongmei
D
Su
Sun
S
Jing
Lina
L
Guan
Qian
Q
Li
Huiling
H
Zhang
Xiaobo
X
Gao
Xu
X
Ma
D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000097577:Homeobox Protein PITX2
D005947:Glucose; D018398:Homeodomain Proteins; D055457:Nodal Protein; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C526007:NODAL protein, human
Nodal; PITX2C; Smad4; cardiomyocyte hypertrophy; glucose à concentration élevée; high glucose; hypertrophie des cardiomyocytes