[High glucose increases periostin expression and the related signal pathway in adult rat cardiac fibroblasts.] [Ariticle in Chinese]
ZOU Ping, WU Li-Ling, WU Dan, FAN Dong, CUI Xiao-Bing, ZHOU Yun, WANG Cheng, LI Li
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China; Department of Pathophysiology, Luzhou Medical College, Luzhou 646000, China
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 pathwayin cardiac fibroblasts. Adult rat cardiac fibroblasts were cultured and stimulated with high glucose (25 mmol/L). The mRNA and proteinexpressions 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 showedthat 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 ofROS in adult rat cardiac fibroblasts, which was reduced by chelerythrine (CLT), a protein kinase C (PKC) inhibitor. High glucoseinducedperiostin 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 glucosefor 30 and 60 min, which was abolished when pretreated with CLT or NAC. SP600125, a specific JNK inhibitor, significantly decreasedperiostin expression induced by high glucose. In conclusion, high glucose stimulates periostin protein expression via a PKC/ROS/JNKdependentpathway in adult rat cardiac fibroblasts.
Key words: high glucose; cardiac fibroblasts; periostin; signal pathway
Received: 2009-12-22 Accepted: 2010-04-02
Corresponding author: 李丽 E-mail: lilyby@163.com
Citing This Article:
ZOU Ping, WU Li-Ling, WU Dan, FAN Dong, CUI Xiao-Bing, ZHOU Yun, WANG Cheng, LI Li. [High glucose increases periostin expression and the related signal pathway in adult rat cardiac fibroblasts.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (3): 247-254 (in Chinese with English abstract).