| Title : Inhibition of soluble epoxide hydrolase ameliorates renal injury in IgA nephropathy by restoring epoxyeicosatrienoic acids - Yin_2026_iScience_29_116200 |
| Author(s) : Yin HH , Fu X , Qiao Q , Yang E , Liu YN , Bai Y , Huang L , Chen YY , Huang ZY , Yu DC , Dai P , Pan QJ , Meng YW , Yin SY , Liu X , Nie S , Deng BQ , He Y , Liu JY |
| Ref : iScience , 29 :116200 , 2026 |
|
Abstract :
Immunoglobulin A (IgA) nephropathy (IgAN) is a major cause of end-stage renal disease with limited therapies. Altered lipid metabolism is implicated in chronic kidney disease, but its role in IgAN is unclear. Plasma oxylipin profiling and renal single-cell RNA sequencing (scRNA-seq) revealed reduced epoxyeicosatrienoic acids (EETs) and increased soluble epoxide hydrolase (sEH) in IgAN. Two sEH inhibitors, t-AUCB and macamide, reduced proteinuria, improved renal function, attenuated IgA deposition, and restored EET levels. Mechanistically, sEH overexpression activated NF-kappaB (p65 phosphorylation) and upregulated TNF-alpha, IL- 6, and IL-1beta; its inhibitors reversed these effects. In human mesangial cells, 14(15)-EET suppressed IgA1-induced NF-kappaB and cytokine expression. Thus, dysregulated lipid peroxidation drives renal inflammation via the NF-kappaB-cytokine axis in IgAN. sEH inhibition stabilizes EETs and preserves renal function, highlighting the sEH-EET axis as a promising therapeutic target. |
| PubMedSearch : Yin_2026_iScience_29_116200 |
| PubMedID: 42256278 |
Yin HH, Fu X, Qiao Q, Yang E, Liu YN, Bai Y, Huang L, Chen YY, Huang ZY, Yu DC, Dai P, Pan QJ, Meng YW, Yin SY, Liu X, Nie S, Deng BQ, He Y, Liu JY (2026)
Inhibition of soluble epoxide hydrolase ameliorates renal injury in IgA nephropathy by restoring epoxyeicosatrienoic acids
iScience
29 :116200
Yin HH, Fu X, Qiao Q, Yang E, Liu YN, Bai Y, Huang L, Chen YY, Huang ZY, Yu DC, Dai P, Pan QJ, Meng YW, Yin SY, Liu X, Nie S, Deng BQ, He Y, Liu JY (2026)
iScience
29 :116200