Roles of heat shock factor 1 in isoproterenol‑induced myocardial fibrosis in mice

Xie,Yong; Zhang,Lihua; Zhang,Bin; Fang,Li

doi:10.3892/mmr.2015.4157

Roles of heat shock factor 1 in isoproterenol‑induced myocardial fibrosis in mice

Authors:
- Yong Xie
- Lihua Zhang
- Bin Zhang
- Li Fang
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Affiliations: Department of General Medicine, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan 423000, P.R. China, Department of Histoembryology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China, Department of Internal Cardiology, Changsha No. 1 People's Hospital, Changsha, Hunan 410078, P.R. China
Published online on: July 30, 2015 https://doi.org/10.3892/mmr.2015.4157
Pages: 5872-5878

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Abstract

Although it is well known that isoproterenol (ISO) causes myocardial hypertrophy and myocardial fibrosis in rats, it has remained elusive whether heat shock factor 1 (HSF1) has a role in this process. The present study aimed to investigate the possible roles of HSF1 in ISO-induced fibrosis in mice. It was found that after administration of ISO in Kunming and HSF1-/+ mice, there was a large number of fibers deposited around blood vessels and among cardiocytes, accompanied with an obvious increase in the protein expressions of type I or III collagen and heat shock protein 47 (HSP47), as indicated by western blot analysis. After intervention with insulin-like growth factor 1 (IGF-1), myocardial fibrosis was significantly attenuated, with a paralleled decrease in the expression of collagen and HSP47 in the mice. However, in HSF1-/- mice, fiber hyperplasy was not observed after injection of ISO, and the levels of type I or III collagen and HSP47 were not significantly increased at the protein and mRNA level. Furthermore, it was demonstrated that after subcutaneous injection of ISO into the back of Kunming and HSF1-/+ mice, large amounts of HSF1 protein were localized to the nucleus, and there was an increase in phosphorylated HSF1 as indicated by western blot and immunohistochemical analysis, respectively. Intervention with IGF-1 inhibited HSF1 activation mediated by ISO. These results suggested that HSF1 is required for myocardial fibrosis in ISO-treated mice, and the underlying molecular mechanism may involve the regulation of HSP47.

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