Cysteine-Rich Protein 61 Plays a Proinflammatory Role in Obstructive Kidney Fibrosis

Lai, Chun-Fu; Chen, Yung-Ming; Chiang, Wen-Chih; Lin, Shuei-Liong; Kuo, Min-Liang; Tsai, Tun-Jun
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Cysteine-rich protein 61 (Cyr61) is a secreted matrix-associated protein that regulates a broad spectrum of biological and cellular activities. This study aimed to investigate the role of Cyr61 in progressive kidney fibrosis induced by unilateral ureteral obstruction (UUO) surgery in mice. The expression of Cyr61 transcripts and proteins in the obstructed kidneys were increased from day 1 and remained high until day 10 after surgery. Immunohistochemistry indicated that Cyr61 was expressed mainly in renal tubular epithelial cells. The upregulated Cyr61 in UUO kidneys was reduced in mice treated with pan-transforming growth factor-β (TGF-β) antibody. The role of TGF-β in tubular Cyr61 upregulation after obstructive kidney injury was further supported by experiments showing that TGF-β1 stimulated Cyr61 expression in cultured tubular epithelial cells. Notably, the upregulation of Cyr61 in UUO kidneys was followed by a marked increase in monocyte chemoattractant protein 1 (MCP-1) transcripts and macrophage infiltration, which were attenuated in mice treated with anti-Cyr61 antibodies. This proinflammatory property of Cyr61 in inducing MCP-1 expression was further confirmed in tubular epithelial cells cultured with Cyr61 protein. The anti-Cyr61 antibody in UUO mice also reduced the levels of collagen type 1-α1 transcripts, collagen fibril accumulation evaluated by picrosirius red staining, and the levels of α-smooth muscle actin (α-SMA) transcripts and proteins on day 4 after surgery; however, the antifibrotic effect was not sustained. In conclusion, the TGF-β-mediated increase in tubular Cyr61 expression involved renal inflammatory cell infiltration through MCP-1 induction during obstructive kidney injury. The Cyr61 blockade attenuated kidney fibrosis in the early phase, but the antifibrotic effect could not be sustained.


Related Articles

  • Reduced NOV/CCN3 Expression Limits Inflammation and Interstitial Renal Fibrosis after Obstructive Nephropathy in Mice. Marchal, Pierre-Olivier; Kavvadas, Panagiotis; Abed, Ahmed; Kazazian, Chantal; Authier, Florence; Koseki, Haruhiko; Hiraoka, Shuichi; Boffa, Jean-Jacques; Martinerie, Cécile; Chadjichristos, Christos E. // PLoS ONE;9/14/2015, Vol. 10 Issue 9, p1 

    The main hallmark of chronic kidney disease (CKD) is excessive inflammation leading to interstitial tissue fibrosis. It has been recently reported that NOV/CCN3 could be involved in kidney damage but its role in the progression of nephropathies is poorly known. NOV/CCN3 is a secreted...

  • Roles of miR-200a in renal fibrosis through regulating ZEB1 and ZEB2. Weisong Wang; Junjie Gao; Fangli Wang // International Journal of Clinical & Experimental Medicine;2016, Vol. 9 Issue 7, p13852 

    Objective: This study aims to investigate the role and mechanism of miR-200a in the epithelial-mesenchymal transition (EMT) of kidney epithelial cells. Methods: Through treatment with transforming growth factor-β1 (TGFβ1), renal epithelial cells HKC were induced to EMT. MiR-200a expression...

  • Oxidative/Nitrative Stress and Inflammation Drive Progression of Doxorubicin-Induced Renal Fibrosis in Rats as Revealed by Comparing a Normal and a Fibrosis-Resistant Rat Strain. Szalay, Csaba Imre; Erdélyi, Katalin; Kökény, Gábor; Lajtár, Enikő; Godó, Mária; Révész, Csaba; Kaucsár, Tamás; Kiss, Norbert; Sárközy, Márta; Csont, Tamás; Krenács, Tibor; Szénási, Gábor; Pacher, Pál; Hamar, Péter // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    Chronic renal fibrosis is the final common pathway of end stage renal disease caused by glomerular or tubular pathologies. Genetic background has a strong influence on the progression of chronic renal fibrosis. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We...

  • Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features. Xu-Dubois, Yi-Chun; Galichon, Pierre; Brocheriou, Isabelle; Baugey, Edith; Morichon, Romain; Jouanneau, Chantal; Ouali, Nacera; Rondeau, Eric; Hertig, Alexandre // Nephrology Dialysis Transplantation;Nov2014, Vol. 29 Issue 11, p2136 

    Background The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial...

  • The kinase Pyk2 is involved in renal fibrosis by means of mechanical stretch-induced growth factor expression in renal tubules. Sonomura, Kazuhiro; Okigaki, Mitsuhiko; Kimura, Taikou; Matsuoka, Eiko; Shiotsu, Yayoi; Adachi, Takaomi; Kado, Hiroshi; Ishida, Ryo; Kusaba, Tetsuro; Matsubara, Hiroaki; Mori, Yasukiyo // Kidney International;Mar2012, Vol. 81 Issue 5, p449 

    Unilateral ureteral obstruction is a well-established experimental model of progressive renal fibrosis. We tested whether mechanical stretch and subsequent renal tubular distension might lead to renal fibrosis by first studying renal tubular epithelial cells in culture. We found that mechanical...

  • Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Grande, M Teresa; Sánchez-Laorden, Berta; López-Blau, Cristina; De Frutos, Cristina A; Boutet, Agnès; Arévalo, Miguel; Rowe, R Grant; Weiss, Stephen J; López-Novoa, José M; Nieto, M Angela // Nature Medicine;Sep2015, Vol. 21 Issue 9, p989 

    Progressive kidney fibrosis contributes greatly to end-stage renal failure, and no specific treatment is available to preserve organ function. During renal fibrosis, myofibroblasts accumulate in the interstitium of the kidney, leading to massive deposition of extracellular matrix and organ...

  • Inhibition of STAT3 acetylation is associated with angiotesin renal fibrosis in the obstructed kidney. Ni, Jun; Shen, Yang; Wang, Zhen; Shao, De-cui; Liu, Jia; Fu, Lan-jun; Kong, Ya-li; Zhou, Li; Xue, Hong; Huang, Yu; Zhang, Wei; Yu, Chen; Lu, Li-min // Acta Pharmacologica Sinica;Aug2014, Vol. 35 Issue 8, p1045 

    Aim:To explore the relationship between the signal transducer and activator of transcription 3 (STAT3) signaling and renal fibrosis.Methods:Rat renal tubular epithelial NRK-52E cells were treated with angiotesin II (Ang II), nicotinamide (an inhibitor of NAD+-dependent class III protein...

  • Akt2 Is Involved in Loss of Epithelial Cells and Renal Fibrosis following Unilateral Ureteral Obstruction. Lan, Aiping; Zhang, Jing; Xiao, Zhicheng; Peng, Xiaogang; Qi, Yongfen; Du, Jie // PLoS ONE;Aug2014, Vol. 9 Issue 8, p1 

    Obstructive nephropathy is an aggressive form of chronic kidney disease (CKD), which is characterized by an epithelial-to-mesenchymal transition (EMT) and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we...

  • MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e. Zhicheng Liu; Yuru Zhou; Yue Yuan; Fang Nie; Rui Peng; Qianyin Li; Zhongshi Lyu; Zhaomin Mao; Liyuan Huang; Li Zhou; Yiman Li; Jing Hao; Dongsheng Ni; Qianni Jin; Yaoshui Long; Pan Ju; Wen Yu; Jianing Liu; Yanxia Hu; Qin Zhou // International Journal of Molecular Sciences;Nov2015, Vol. 16 Issue 11, p27945 

    Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics