WNT1-inducible-signaling pathway protein 1 regulates the development of kidney fibrosis through the TGF-β1 pathway

被引：18
作者：
Wang, Bo [1 ,2 ]
Ding, Xiaoming [1 ]
Ding, Chenguang [1 ]
Tesch, Greg [3 ,4 ]
Zheng, Jin [1 ]
Tian, PuXun [1 ]
Ricardo, Sharon [5 ]
Shen, Hsin-Hui [2 ]
Xue, Wujun [1 ]
机构：
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Nephropathy Hosp, Dept Kidney Transplantat, Xian 710061, Shaanxi, Peoples R China
[2] Monash Univ, Dept Mat Sci & Engn, Clayton, Vic, Australia
[3] Monash Univ, Dept Nephrol, Clayton, Vic, Australia
[4] Monash Med Ctr, Dept Med, Clayton, Vic, Australia
[5] Monash Univ, Dept Pharmacol, Monash Biomed Discovery Inst, Clayton, Vic, Australia
来源：
FASEB JOURNAL | 2020年 / 34卷 / 11期
基金：
中国国家自然科学基金;
关键词：
kidney fibrosis; TGF-beta; 1; WISP1; UUO model; MESENCHYMAL STEM-CELLS; TGF-BETA; RENAL FIBROSIS; GROWTH-FACTOR; WISP-1; WNT; PROLIFERATION; FIBROGENESIS; BLOCKADE; THERAPY;
D O I：
10.1096/fj.202000953R
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：
Fibrosis is a pathological feature of chronic kidney disease and its progression correlates with declining renal function. Kidney fibrosis is driven by multiple profibrotic factors. This project examined the regulatory function of WNT1-inducible-signaling pathway protein 1 (WISP1) in the development of kidney fibrosis. Induction of WISP1 by transforming growth factor beta 1 (TGF-beta 1), and the role of WISP1 in TGF-beta 1/Smad signaling and fibrotic responses, was examined in multiple kidney cells. Kidney expression of WISP1 was examined in mouse models of unilateral ureter obstruction (UUO) and streptozotocin-induced diabetic nephropathy. WISP1 antibody was administered to UUO mice during the induction of kidney injury and the impact on kidney fibrosis was examined. WISP1 expression was upregulated in both mouse models. TGF-beta 1-induced expression of WISP1 and profibrotic genes in cultured kidney cells via TGF-beta R1. Recombinant WISP1-induced expression of TGF-beta R1 in kidney cells. Suppression of WISP1 by shRNA or neutralizing antibody reduced TGF-beta 1-mediated activation of Smad3, fibrotic gene expression, and fibroblast proliferation. Treatment with WISP1 antibody inhibited the development of kidney fibrosis in UUO mice. WISP1 mediates the profibrotic effects of TGF-beta 1 in kidney cells and in kidney disease. Pharmacological blockade of WISP1 exhibits potential as a novel therapy for inhibiting kidney fibrosis.
引用
收藏
页码：14507 / 14520
页数：14
相关论文
共 37 条
  • [1] Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis
    Chow, FY
    Nikolic-Paterson, DJ
    Atkins, RC
    Tesch, GH
    [J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 2004, 19 (12) : 2987 - 2996
  • [2] Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor
    Colston, J. T.
    de la Rosa, S. D.
    Koehler, M.
    Gonzales, K.
    Mestril, R.
    Freeman, G. L.
    Bailey, S. R.
    Chandrasekar, B.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 293 (03): : H1839 - H1846
  • [3] Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog
    Edeling, Maria
    Ragi, Grace
    Huang, Shizheng
    Pavenstaedt, Hermann
    Susztak, Katalin
    [J]. NATURE REVIEWS NEPHROLOGY, 2016, 12 (07) : 426 - 439
  • [4] Deletion of nicotinamide nucleotide transhydrogenase - A new quantitive trait locus accounting for glucose intolerance in C57BL/6J mice
    Freeman, Helen C.
    Hugill, Alison
    Dear, Neil T.
    Ashcroft, Frances M.
    Cox, Roger D.
    [J]. DIABETES, 2006, 55 (07) : 2153 - 2156
  • [5] WISP-1 is an osteoblastic regulator expressed during skeletal development and fracture repair
    French, DM
    Kaul, RJ
    D'Souza, AL
    Crowley, CW
    Bao, M
    Frantz, GD
    Filvaroff, EH
    Desnoyers, L
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2004, 165 (03) : 855 - 867
  • [6] Blockade of Smad signaling by 3′-deoxyadenosine: a mechanism for its anti-fibrotic potential
    Gu, Liubao
    Johno, Hisashi
    Nakajima, Shotaro
    Kato, Hironori
    Takahashi, Shuhei
    Katoh, Ryohei
    Kitamura, Masanori
    [J]. LABORATORY INVESTIGATION, 2013, 93 (04) : 450 - 461
  • [7] Wnt/β-Catenin Signaling Promotes Renal Interstitial Fibrosis
    He, Weichun
    Dai, Chunsun
    Li, Yingjian
    Zeng, Gang
    Monga, Satdarshan P.
    Liu, Youhua
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (04): : 765 - 776
  • [8] Combination therapy of mesenchymal stem cells and serelaxin effectively attenuates renal fibrosis in obstructive nephropathy
    Huuskes, Brooke M.
    Wise, Andrea F.
    Cox, Alison J.
    Lim, Ee X.
    Payne, Natalie L.
    Kelly, Darren J.
    Samuel, Chrishan S.
    Ricardo, Sharon D.
    [J]. FASEB JOURNAL, 2015, 29 (02) : 540 - 553
  • [9] Pathogenesis of fibrosis:: role of TGF-β and CTGF
    Ihn, H
    [J]. CURRENT OPINION IN RHEUMATOLOGY, 2002, 14 (06) : 681 - 685
  • [10] Wnt-Induced Secreted Protein 1/CCN4 in Liver Fibrosis Both in vitro and in vivo
    Jian, Yi-Cheng
    Wang, Jin-Jun
    Dong, Shuang
    Hu, Jun-Wei
    Hu, Li-Juan
    Yang, Gen-Mei
    Zheng, Ya-Xin
    Xiong, Wu-Jun
    [J]. CLINICAL LABORATORY, 2014, 60 (01) : 29 - 35
1234