caa a22 4500 606235620 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2456-5 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2456-5 Fluorofenidone protects against renal fibrosis by inhibiting STAT3 tyrosine phosphorylation [Elektronische Daten] [Juan Tang, Chun-yan Liu, Miao-miao Lu, Jing Zhang, Wen-juan Mei, Wen-jun Yang, Yan-yun Xie, Ling Huang, Zhang-zhe Peng, Qiong-jing Yuan, Ji-shi Liu, Gao-yun Hu, Li-jian Tao] Signaling through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, especially JAK2/STAT3, is involved in renal fibrosis. Fluorofenidone (FD), a novel pyridone agent, exerts anti-fibrotic effects in vitro and in vivo. Herein, we sought to investigate whether FD demonstrates its inhibitory function through preventing JAK2/STAT3 pathway. In this study, we examined the effect of FD on activation of rat renal interstitial fibroblasts, glomerular mesangial cells (GMC), and expression of JAK2/STAT3. Moreover, we explored the histological protection effects of FD in UUO rats, db/db mice, and phosphorylation of JAK2/STAT3 cascade. Our studies found that pretreatment with FD resulted in blockade of activation of fibroblast and GMC manifested by fibronectin (FN) and α-smooth muscle actin (α-SMA) protein expression and decline of STAT3 tyrosine phosphorylation induced by IL-6 or high glucose. In unilateral ureteral obstruction rats and a murine model of spontaneous type 2 diabetes (db/db mice), treatment with FD blocked the expression of FN and α-SMA, prevented renal fibrosis progression, and attenuated STAT3 activation. However, FD administration did not interfere with JAK2 activation both in vivo and in vitro. In summary, the molecular mechanism by which FD exhibits renoprotective effects appears to involve the inhibition of STAT3 phosphorylation. Springer Science+Business Media New York, 2015 Fluorofenidone nationallicence Fibrosis nationallicence JAK2/STAT3 pathway nationallicence Obstructive nephropathy nationallicence Diabetic nephropathy nationallicence Tang Juan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Liu Chun-yan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Lu Miao-miao Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Zhang Jing Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Mei Wen-juan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Yang Wen-jun Division of Endocrinology, Xiangya Third Hospital, Central South University, 410013, Changsha, Hunan, China aut Xie Yan-yun Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Huang Ling Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Peng Zhang-zhe Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Yuan Qiong-jing Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Liu Ji-shi Division of Nephrology, Xiangya Third Hospital, Central South University, 410013, Changsha, Hunan, China aut Hu Gao-yun Department of Medical Chemistry, School of Pharmacy, Central South University, 410008, Changsha, Hunan, China aut Tao Li-jian Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 77-87 0300-8177 407:1-2<77 2015 407 11010 https://doi.org/10.1007/s11010-015-2456-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2456-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tang Juan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Liu Chun-yan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Lu Miao-miao Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Zhang Jing Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Mei Wen-juan Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Yang Wen-jun Division of Endocrinology, Xiangya Third Hospital, Central South University, 410013, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Xie Yan-yun Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Huang Ling Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Peng Zhang-zhe Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Yuan Qiong-jing Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Liu Ji-shi Division of Nephrology, Xiangya Third Hospital, Central South University, 410013, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Hu Gao-yun Department of Medical Chemistry, School of Pharmacy, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Tao Li-jian Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 77-87 0300-8177 407:1-2<77 2015 407 11010