Abstract:
Elevated levels of circulating fibroblast growth factor 21 (FGF21) have been reported in patients with hyperuricemia. However, the effect of FGF21 in hyperuricemic nephropathy (HN) remains unexplored. Here, we investigated the effect and mechanism of action of FGF21 on HN. HN model was induced with adenine and potassium oxysalt in wild-type C57BL/6 mice and FGF21?/? mice. For in vitro studies, human renal tubular epithelial (HK-2) cells were exposed to uric acid with/without FGF21 or ?-Klotho-siRNA. Here, we reported aggravated renal dysfunction and structural damage in the FGF21?/? mice compared to the wild-type mice. These were evident in the upsurge of inflammatory factors IL-1?, TNF-?, IL-6, and IL-18; fibrotic markers Collagen I and ?-SMA; and oxidation products ROS and MDA. However, exogenous administration of FGF21 to wild-type HN mice significantly reversed these negative effects. In terms of mechanism, FGF21 significantly inhibited NF-?B/NLRP3 and TGF-?1/Smad3 pathways and promoted nuclear translocation of Nrf2 both in vivo and in vitro. Furthermore, the silencing of ?-Klotho was marked by the attenuation of the improved effect of FGF21 on cell damage. In conclusion, our studies revealed that exogenous FGF21 treatment significantly improved HN, which was achieved by the inhibition of inflammation, fibrosis, and oxidative stress. � 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
Description:
Jiang, X., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Wu, Q., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Opoku, Y.K., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China, Department of Biology Education, Faculty of Science Education, University of Education, Winneba, Ghana; Zou, Y., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Wang, D., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Hu, C., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Ren, G., Biopharmaceutic Lab, College of Life Science, Northeast Agricultural University, Harbin, China, Key Laboratory of Agricultural Biological Function Gene, Northeast Agricultural University, Harbin, China