High glucose induces Rho/ROCK-dependent visfatin and type I procollagen expression in rat primary cardiac fibroblasts

Yang,Rong; Chang,Liang; Liu,Suyun; Jin,Xin; Li,Yongjun

doi:10.3892/mmr.2014.2408

High glucose induces Rho/ROCK-dependent visfatin and type I procollagen expression in rat primary cardiac fibroblasts

Authors:
- Rong Yang
- Liang Chang
- Suyun Liu
- Xin Jin
- Yongjun Li
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Affiliations: Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei 050000, P.R. China
Published online on: July 22, 2014 https://doi.org/10.3892/mmr.2014.2408
Pages: 1992-1998

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Abstract

Myocardial fibrosis and excessive proliferation of cardiac fibroblasts (CFs) contribute to diabetic cardiomyopathy (DCM). However, the underlying mechanism is still not completely clear. The aim of this study was to investigate the relationship between high-glucose treatment and the expression of visfatin and type I procollagen in rat CFs, and examine the regulatory effects of high‑glucose treatment on the Rho/ROCK signaling pathway. CFs from newborn Sprague Dawley rats were treated with high concentrations of glucose (10, 30 and 50 mmol/l D-glucose), a baseline concentration of glucose (5.5 mmol/l) as a control, and mannitol (5.5 mmol/l D-glucose + 44.5 mmol/l mannitol) as an osmotic control. CFs were also treated with 30 mmol/l D-glucose for 6, 12, 24 and 48 h. The proliferation of CFs was determined by the MTT assay. The mRNA and protein expression of visfatin and type I procollagen were quantified by RT-qPCR and western blot analysis, respectively. Cardiac fibroblast proliferation reached a peak at 30 mmol/l D-glucose, and visfatin and type I procollagen expression were significantly increased upon treatment with high concentrations of glucose (10 and 30 mmol/l) compared to baseline glucose treatment. Treatment with 30 mmol/l D-glucose time-dependently promoted cardiac fibroblast proliferation. The mRNA and protein expression of visfatin and type I procollagen were significantly increased compared to the control at 24 h after 30 mmol/l D-glucose treatment. Y27632, a Rho-associated protein kinase (ROCK) inhibitor, significantly decreased the mRNA and protein levels of visfatin and type I procollagen, induced by 30 mmol/l D-glucose (all P<0.05). In conclusion, a high level of glucose promotes cardiac fibroblast proliferation, and induces visfatin and type I procollagen expression in CFs, at least partially via the Rho/ROCK signaling pathway. These results may be helpful in developing an appropriate therapeutic strategy for DCM.

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