Inhibition of STAT3 acetylation is associated with attenuated renal fibrosis in the obstructed kidney

• Published in: Acta pharmacologica Sinica Vol. 35; no. 8; pp. 1045 - 1054
• Main Authors: Ni, Jun, Shen, Yang, Wang, Zhen, Shao, De-cui, Liu, Jia, Fu, Lan-jun, Kong, Ya-li, Zhou, Li, Xue, Hong, Huang, Yu, Zhang, Wei, Yu, Chen, Lu, Li-min
• Format: Journal Article
• Language: English
• Published: 30.06.2014
• Subjects: STAT3; 乙酰化; 梗阻; 纤连蛋白; 肾脏; 肾间质纤维化; 胶原蛋白; 血管紧张素
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2014.42.

Aim： To explore the relationship between the signal transducer and activator of transcription 3 （STAT3） signaling and renal fibrosis Methods： Rat renal tubular epithelial NRK-52E cells were treated with angiotensin Ⅱ （Ang Ⅱ）, nicotinamide （an inhibitor of NAD＋- dependent class ⅡI protein deacetylases, SIRT1-7）, or resveratro obstruction （UUO） were used for in vivo studies. Renal interstitial STAT3 acetylation and phosphorylation, fibronectin, collagen I, co （an activator of SIRT1）. Mice underwent unilateral uretera fibrosis was observed with HE and Masson＇s trichrome staining. lagen Ⅳ, and α-smooth muscle actin （α-SMA） levels were examined using Western blotting. Results： Nicotinamide （0.625-10 mmol/L） dose-dependently increased STAT3 acetylation on Lys685 and phosphorylation on Tyr705 in NRK-52E cells, accompanied by accumulation of fibronectin and collagen Ⅳ. Ang Ⅱ increased STAT3 phosphorylation on Tyr705 and the expression of fibronectin, collagen Ⅳ and α-SMA in the cells. Pretreatment with resveratrol （12.5 μmol/L） blocked Ang Ⅱ-induced effects in the cells. UUO induced marked STAT3 phosphorylation, fibronectin, collagen Ⅳ and α-SMA accumulation, and renal interstitial fibrosis in the obstructed kidneys, which were significantly attenuated by daily administration of resveratrol （100 mg/kg）. Conclusion： STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.