High Glucose and Matrix Formation in Atrial Myocytes

  • Chang, Jen-Ping (PI)
  • Chen, Mien Cheng (CoPI)
  • Huang, Hsien Da (CoPI)
  • Wang, Pei-Wen (CoPI)
  • Wang, Feng Sheng (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Type 2 diabetes mellitus (DM) is the most prevalent and serious metabolic disease worldwide. Diabetes mellitus is one of the independent risk factors for development of atrial fibrillation (AF). Atrial fibrosis, an important mechanism of permanent AF, is frequently observed in the atrial myocardium of permanent AF patients. Till now, there is no effective treatment to prevent atrial fibrosis. Therefore, the investigation of the molecular mechanisms by which DM might lead to atrial fibrosis is important to improve the management of patients with DM. Transforming growth factor-β signaling has been shown to act as a pivotal mechanism for increased cardiac fibrosis. Transforming growth factor-β is also known to stimulate fibronectin production by various cells. Insoluble cellular fibronectin is a major component of the extracellular matrix or fibrosis. Cultured atrial-derived myocytes have been shown to secret transforming growth factor-β in response to tachypacing. However, transforming growth factor-β and fibronectin synthesized by the cultured atrial-derived myocytes in response to high glucose and high osmolality stimuli have never been studied. In our pilot study, we found that high glucose increased transforming growth factor-β and fibronectin in cultured atrial-derived myocytes cultures independently of angiotensin II type 1 receptor. Interestingly, microRNA-377 (miRNA-377) has been shown to regulate translation of the genes related to fibronectin production in cultured human and mouse mesangial cells to high glucose and transforming growth factor-β stimulation. Therefore, we hypothesized that miRNAs might play a role in the regulation of fibronectin production by the cultured atrial-derived myocytes in response to high glucose stimulus. Posttranslational mechanisms, such as the miRNA, have been increasingly recognized as key modulators of metabolic function and in the pathogenesis of type 2 diabetes. According, posttranslational mechanisms, such as the miRNA and mRNA expression profiling, might play a critical role in the biological processes in cultured atrial-derived myocytes cultures in response to high glucose stimulus. Microarray analysis allows us to search systemically RNA expression profiling in tissues and culture cells. One major benefit of microarray analysis of gene expression is that it can be used to discover associating genes that were previously thought to be unrelated to a pathological event. Moreover, commercially available biological database and software can be used for functional network analysis. In this study, we will use microarray analysis, biological database, and functional network analysis software to present a comprehensive picture of the expression profiling of miRNAs and mRNA in the cell lysates of cultured atrial-derived myocytes cultures in response to high glucose stimulus. With the accomplishment of this project, we can systemically uncover important biological pathways for extracellular matrix production by cultured atrial-derived myocytes. The findings of this project can provide important new insights for future studies to investigate potential drugs to prevent atrial fibrosis, an important mechanism of permanent AF, in diabetes mellitus.

Project IDs

Project ID:PC10108-0275
External Project ID:NSC101-2314-B182-011
StatusFinished
Effective start/end date01/08/1231/07/13

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.