Nimbolide ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibition of TGF-beta and EMT/Slug signalling

被引：40

作者：

Annaldas, Shivaraju ^{[1
]}

Saifi, Mohd Aslam ^{[1
]}

Khurana, Amit ^{[1
]}

Godugu, Chandraiah ^{[1
]}

机构：

[1] NIPER, Dept Regulatory Toxicol, Hyderabad 500037, Telangana, India

来源：

MOLECULAR IMMUNOLOGY | 2019年 / 112卷

关键词：

Chronic kidney disease; Epithelial-mesenchymal transition; Nimbolide; Renal fibrosis; TGF-beta; EPITHELIAL-MYOFIBROBLAST TRANSDIFFERENTIATION; OXIDATIVE STRESS; MESENCHYMAL TRANSITION; HEPATIC-FIBROSIS; CARDIAC FIBROSIS; RATS; INDUCTION; NANOCERIA; REDUCTION; APOPTOSIS;

D O I：

10.1016/j.molimm.2019.06.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chronic kidney disease (CKD) involves interstitial fibrosis as an underlying pathological process associated with compromised renal function irrespective of etiological cause of the injury. The transforming growth factor-13 (TGF-beta) plays a pivotal role in progression of renal fibrosis. TGF-beta transduces its downstream signalling by phosphorylation of smad2/3 and also regulates epithelial-mesenchymal-transition (EMT), a program centrally involved in activation of fibroblasts. Renal fibrosis was induced in Swiss albino mice by unilateral ureteral obstruction of animals. Kidney tissues were evaluated for fibrotic protein expression by western blot and immunohistochemistry. The administration of nimbolide (NB) to UUO animals reduced the oxidative stress, expression of ECM proteins, TGF-beta, p-smad and EMT program. Further, NB administration also improved histoarchitecture of obstructed kidney and reduced the collagen deposition in kidney. Our results provided compelling evidence to support antifibrotic activity of NB by reduction in oxidative stress, TGF-beta, and EMT program in fibrotic kidney. The administration of NB in animals blunted the UUO-induced renal injury, inflammation and reduced fibrogenesis in obstructed kidney.

引用

页码：247 / 255

页数：9

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