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Fluorofenidone inhibits nicotinamide adeninedinucleotide phosphate oxidase via PI3K/Akt pathway in the pathogenesis of renal interstitial fibrosis
Author(s) -
Qin Jiao,
Xie Yanyun,
Huang Ling,
Yuan Qiongjing,
Mei WenJuan,
Yuan Xiangning,
Hu Gaoyun,
Cheng Guangjie,
Tao Lijian,
Peng Zhangzhe
Publication year - 2013
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12128
Subject(s) - medicine , pathogenesis , pi3k/akt/mtor pathway , fibrosis , protein kinase b , nadph oxidase , cancer research , microbiology and biotechnology , signal transduction , oxidative stress , biology
Aim Oxidative stress plays an important role in the progression of renal interstitial fibrosis. The nicotinamide adeninedinucleotide phosphate ( NADPH ) oxidase ( N ox) family is considered one of the major sources of reactive oxygen species ( ROS ). In the present study, we investigated the inhibitory effects of a novel anti‐fibrotic agent, Fluorofenidone ( AKF‐PD ), upon N ox‐mediated oxidative stress and deposition of extracellular matrix ( ECM ) in the development of renalinterstitial fibrosis. Methods AKF‐PD was used to treat renal fibrosis in unilateral ureteral obstruction ( UUO ) obstructive nephropathy in rats. The expression of Nox homologues, p‐ A kt, collagen I and III were detected by immunoblotting or immunohistochemistry. Levels of 8‐iso prostaglandin F 2alpha (8‐ I so PGF2a ) was measured by enzyme linked immunosorbent assay. In addition, ROS and the expression of collagen I (1a), Nox subunits and p‐ A kt was measured in angiotensin ( A ng) II ‐stimulated rat proximal tubular epithelial ( NRK‐52E ) cells in culture. Results AKF‐PD treatment significantly attenuated tubulo‐interstitial injury, ECM deposition and oxidative stress in fibrotic rat kidneys. In addition, AKF‐PD inhibited the expression of ROS , Collagen I (1a), N ox2, p‐ A kt in A ng II ‐stimulated NRK ‐52 E cells. Conclusion AKF‐PD attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and ECM deposition via the PI3K/Akt signalling pathway, suggesting AKF‐PD is a potential novel therapeutic agent against renal fibrosis.