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Tubulointerstitial fibrosis is an inevitable consequence of all progressive chronic kidney disease (CKD) and contributes to a substantial health burden worldwide. Icariin, an active flavonoid glycoside obtained from Epimedium species, exerts potential antifibrotic effect. The study aimed to explore the protective effects of icariin against tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO)-induced CKD mice and TGF-β1-treated HK-2 cells, and furthermore, to elucidate the underlying mechanisms. The results demonstrated that icariin significantly improved renal function, alleviated tubular injuries, and reduced fibrotic lesions in UUO mice. Furthermore, icariin suppressed renal inflammation, reduced oxidative stress as evidenced by elevated superoxide dismutase activity and decreased malondialdehyde level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was restored by icariin. In HK-2 cells treated with TGF-β1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with preserving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway both in vivo and in vitro, whereas inhibition of Nrf2 by ML385 counteracted the protective effects of icariin on TGF-β1-induced HK-2 cells. In conclusion, icariin protects against renal inflammation and tubulointerstitial fibrosis at least partly through Nrf2-mediated attenuation of mitochondrial dysfunction, which suggests that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.

Titel:	Icariin alleviates renal inflammation and tubulointerstitial fibrosis via Nrf2-mediated attenuation of mitochondrial damage.
Autor/in / Beteiligte Person:	Ding, N ; Sun, S ; Zhou, S ; Lv, Z ; Wang, R
Link:	Zum Volltext
Zeitschrift:	Cell biochemistry and function, Jg. 42 (2024-04-01), Heft 3, S. e4005
Veröffentlichung:	Oxford, England : Wiley-Blackwell ; <i>Original Publication</i>: Guildford, Surrey : Butterworth Scientific Ltd., c1983-, 2024
Medientyp:	academicJournal
ISSN:	1099-0844 (electronic)
DOI:	10.1002/cbf.4005
Schlagwort:	Mice Animals Kidney metabolism Transforming Growth Factor beta1 metabolism NF-E2-Related Factor 2 metabolism Reactive Oxygen Species metabolism Flavonoids pharmacology Fibrosis Inflammation metabolism Ureteral Obstruction metabolism Ureteral Obstruction pathology Renal Insufficiency, Chronic drug therapy
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Grant Information: NO: 202201-075 Shandong First Medical University Contributed Indexing: Keywords: Nrf2 pathway; icariin; mitochondrial dysfunction; oxidative stress; renal tubulointerstitial fibrosis Substance Nomenclature: 0 (Transforming Growth Factor beta1) ; VNM47R2QSQ (icariin) ; 0 (NF-E2-Related Factor 2) ; 0 (Reactive Oxygen Species) ; 0 (Flavonoids) Entry Date(s): Date Created: 20240407 Date Completed: 20240408 Latest Revision: 20240408 Update Code: 20240408

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Icariin alleviates renal inflammation and tubulointerstitial fibrosis via Nrf2-mediated attenuation of mitochondrial damage.