title: [High glucose increases periostin expression and the related signal pathway in adult rat cardiac fibroblasts].
abstract: Cardiac fibrosis is a major mechanism contributing to myocardial systolic and diastolic dysfunction in diabetic cardiomyopathy. Periostin is a novel extracellular matrix protein, secreted from cardiac fibroblasts, and closely related with cardiac fibrosis and remodeling. The present study aimed to investigate the effect of high glucose on periostin expression and the related signal transduction pathway in cardiac fibroblasts. Adult rat cardiac fibroblasts were cultured and stimulated with high glucose (25 mmol/L). The mRNA and protein expressions of periostin were detected by RT-PCR and Western blot, respectively. Intracellular reactive oxygen species (ROS) production was measured using 2, 7-dichlorofluorescein diacetate (DCF-DA), an oxidant-sensitive fluorescent probe. Results showed that the mRNA expression of periostin in adult rat cardiac fibroblasts was increased by 117.26% when treated with high glucose for 12 h. Incubation with high glucose for 24 h enhanced periostin protein expression by up to 93.12%. High glucose induced the production of ROS in adult rat cardiac fibroblasts, which was reduced by chelerythrine (CLT), a protein kinase C (PKC) inhibitor. High glucose-induced periostin protein expression was decreased significantly when pretreated with CLT or N-acetylcysteine (NAC), a ROS scavenger. The phosphorylation of c-jun N-terminal protein kinase (JNK) was increased markedly when stimulated with high glucose for 30 and 60 min, which was abolished when pretreated with CLT or NAC. SP600125, a specific JNK inhibitor, significantly decreased periostin expression induced by high glucose. In conclusion, high glucose stimulates periostin protein expression via a PKC/ROS/JNK-dependent pathway in adult rat cardiac fibroblasts.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Wu
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.forename: Dong
authors.initials: D
authors.lastname: Fan
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cui
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D003470:Culture Media; C512836:Postn protein, rat; D017382:Reactive Oxygen Species; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose; D000111:Acetylcysteine