Geniposide suppresses phenotypic transformation of neonatal rat cardiac fibroblasts into myofibroblasts induced by high glucose
Received:April 22, 2019  
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DOI:10.11915/j.issn.1671-5403.2019.09.151
Key words:geniposide  high glucose  cardiac fibroblast  diabetic cardiomyopathy
Author NameAffiliationE-mail
XIANG Jia-Pei Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China  
LEI Yu-Hua Department of Cardiology, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China huayulei_0319@126.com 
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Abstract:
      Objective To investigate the effect of geniposide (GE) on phenotypic transformation of neonatal rat cardiac fibroblasts (CF) as well as on collagen synthesis under the induction of high glucose (HG), and explore the underlying mechanisms. Methods Primary CF were extracted from neonatal rats, and then treated in presence or absence of 33.3mmol/L HG or GE for 24h. The mRNA levels of collagen Ⅰ (Col I), collagen Ⅲ (Col Ⅲ) and connective tissue growth factor (CTGF)were detected by reverse transcription-polymerase chain reaction (RT-PCR). The markers of oxidative stress, including superoxide dismutase (SOD), reduced nicotinamide adenine dinucleotide phosphate (NADPH) and malondialdehyde (MDA) were measured by corresponding test kits. The protein levels of transforming growth factor-beta (TGF-β), acetylated-Smad3 (ac-Smad3), α-smooth muscle actin (SMA) and silent information regulator 1 (SIRT1) were detected using Western blotting. After SIRT1 inhibitor, EX-527 was added, the expression of SIRT1 and α-SMA, activities and production of oxidative stress markers, and protein levels of ac-Smad3 signal pathway related proteins were observed and measured to further explore the protective mechanisms of GE. SPSS 22.0 statistics was used to analyze the data. Results Treatment of GE at different concentrations (1-100μmol/L) for 24h resulted in decreased mRNA levels of Col Ⅰ, Col Ⅲ and CTGF in a dose-dependent manner. Meantime, GE significantly reduced the activity of NADPH, decreased the production of MDA and enhanced the activity of SOD in the process of HG induction. Western blotting indicated that HG treatment induced up-regulation of TGF-β, ac-Smad3 and α-SMA, while GE obviously inhibited the elevations and reversed the down-regulation of SIRT1 induced by HG. Immunofluorescence assay showed that the inhibitor EX-527 could block the inhibitory effect of GE on HG-induced α-SMA and oxidative stress. Conclusion GE exerts inhibitory effect on high HG-induced phenotypic transformation of CF as well as collagen synthesis, which may be associated with TGF-β/ac-Smad3 signal pathway and oxidative stress mediated by SIRT1.
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