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

共 62 条

[31] Cardioprotective effects of nanoceria in a murine model of cardiac remodeling [J].

Kumari, Preeti ;

Saifi, Mohd Aslam ;

Khurana, Amit ;

Godugu, Chandraiah .

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 2018, 50 :198-208

[32] Potential Therapeutic Targets for Cardiac Fibrosis TGFβ, Angiotensin, Endothelin, CCN2, and PDGF, Partners in Fibroblast Activation [J].

Leask, Andrew .

CIRCULATION RESEARCH, 2010, 106 (11) :1675-1680

[33] Mechanistic connection between inflammation and fibrosis [J].

Lee, Soo Bong ;

Kalluri, Raghu .

KIDNEY INTERNATIONAL, 2010, 78 :S22-S26

[34] Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis [J].

Lemos, Dario R. ;

McMurdo, Michael ;

Karaca, Gamze ;

Wilflingseder, Julia ;

Leaf, Irina A. ;

Gupta, Navin ;

Miyoshi, Tomoya ;

Susa, Koichiro ;

Johnson, Bryce G. ;

Soliman, Kirolous ;

Wang, Guanghai ;

Morizane, Ryuji ;

Bonventre, Joseph V. ;

Duffield, Jeremy S. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2018, 29 (06) :1690-1705

[35] Blockade of Endothelial-Mesenchymal Transition by a Smad3 Inhibitor Delays the Early Development of Streptozotocin-Induced Diabetic Nephropathy [J].

Li, Jinhua ;

Qu, Xinli ;

Yao, Jun ;

Caruana, Georgina ;

Ricardo, Sharon D. ;

Yamamoto, Yasuhiko ;

Yamamoto, Hiroshi ;

Bertram, John F. .

DIABETES, 2010, 59 (10) :2612-2624

[36] Oxidative stress and glutathione in TGF-β-mediated fibrogenesis [J].

Liu, R. -M. ;

Pravia, K. A. Gaston .

FREE RADICAL BIOLOGY AND MEDICINE, 2010, 48 (01) :1-15

[37] Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis [J].

Lovisa, Sara ;

LeBleu, Valerie S. ;

Tampe, Bjorn ;

Sugimoto, Hikaru ;

Vadnagara, Komal ;

Carstens, Julienne L. ;

Wu, Chia-Chin ;

Hagos, Yohannes ;

Burckhardt, Birgitta C. ;

Pentcheva-Hoang, Tsvetelina ;

Nischal, Hersharan ;

Allison, James P. ;

Zeisberg, Michael ;

Kalluri, Raghu .

NATURE MEDICINE, 2015, 21 (09) :998-+

[38] Role of Nrf2 in Oxidative Stress and Toxicity [J].

Ma, Qiang .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013, 2013, 53 :401-+

[39] TGF-β: the master regulator of fibrosis [J].

Meng, Xiao-ming ;

Nikolic-Paterson, David J. ;

Lan, Hui Yao .

NATURE REVIEWS NEPHROLOGY, 2016, 12 (06) :325-338

[40] Fibroblasts and myofibroblasts in renal fibrosis [J].

Meran, Soma ;

Steadman, Robert .

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2011, 92 (03) :158-167

← 1 2 3 4 5 6 7 →