| First Author | Liu X | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 479 |
| Issue | 1 | Pages | 109-15 |
| PubMed ID | 27634219 | Mgi Jnum | J:239133 |
| Mgi Id | MGI:5824977 | Doi | 10.1016/j.bbrc.2016.09.050 |
| Citation | Liu X, et al. (2016) Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice. Biochem Biophys Res Commun 479(1):109-15 |
| abstractText | 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 beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-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-beta1, and alpha-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-beta1/Smads, MMP activities, and alpha-SMA expression in diabetic mice. |
