Nimbolide ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibition of TGF-beta and EMT/Slug signalling
Nimbolide ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibition of TGF-beta and EMT/Slug signalling
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DOI：
10.1016/j.molimm.2019.06.003
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发表时间：
2019-08-01
影响因子：
3.6
通讯作者：
Godugu, Chandraiah
中科院分区：
文献类型：
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作者：
Annaldas, Shivaraju;Saifi, Mohd Aslam;Godugu, Chandraiah
慢性肾脏病（CKD）涉及间质纤维化，这是一种与肾功能受损相关的潜在病理过程，无论损伤的病因如何。转化生长因子-13（TGF-β）在肾纤维化的进展中起关键作用。TGF-β通过smad 2/3的磷酸化转导其下游信号传导，并且还调节上皮-间充质转化（EMT），这是一种主要参与成纤维细胞活化的程序。通过单侧输尿管梗阻诱导Swiss白化病小鼠肾纤维化。通过蛋白质印迹和免疫组织化学评价肾组织的纤维化蛋白表达。Nimbolide（NB）可降低UUO动物的氧化应激、ECM蛋白、TGF-β、p-smad和EMT程序的表达。此外，NB给药还改善了梗阻肾脏的组织结构，减少了肾脏中的胶原沉积。我们的研究结果提供了令人信服的证据，支持NB的抗纤维化活性，减少氧化应激，TGF-β和EMT计划在纤维化肾脏。在动物中给予NB可减弱UUO诱导的肾损伤、炎症和减少阻塞肾中的纤维化。
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.