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Author Liu, Xue ♦ Liang, Ershun ♦ Song, Xiuhui ♦ Du, Zhanhui ♦ Zhang, Yun ♦ Zhao, Yuxia
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ FIBROSIS ♦ GROWTH FACTORS ♦ INHIBITION ♦ MATRICES ♦ MICE ♦ PLANT GROWTH
Abstract Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl–prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone. Pin1 inhibition alleviates cardiac fibrosis and dysfunction. In vitro, high glucose increases Pin1 expression with an accompanying increase in phospho-Akt (Ser 473), p-Smad2, p-Smad3, TGF-β1, and α-SMA in cardiac fibroblasts (CFs). These increases are effectively prevented by the inhibition of Pin1 by juglone. Furthermore, Pin1 inhibition inhibits HG-induced CF proliferation and migration. Our results indicate that Pin1 inhibition attenuates cardiac extracellular matrix deposition by regulating the phosphorylation of Akt, TGF-β1/Smads, MMP activities, and α-SMA expression in diabetic mice.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-10-07
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 479
Issue Number 1


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