Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in Mesangial Proliferative Glomerulonephritis Models

被引：24

作者：

Bai, Jiuxu ^{[1
]}

Wu, Lingling ^{[1
]}

Chen, Xiaoniao ^{[2
]}

Wang, Liqiang ^{[2
]}

Li, Qinggang ^{[1
]}

Zhang, Yingjie ^{[1
]}

Wu, Jie ^{[1
]}

Cai, Guangyan ^{[1
]}

Chen, Xiangmei ^{[1
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Chinese PLA Inst Nephrol, Natl Clin Res Ctr Kidney Dis, State Key Lab Kidney Dis,Dept Nephrol, Beijing, Peoples R China

[2] Chinese Peoples Liberat Army Gen Hosp, Dept Ophthalmol, Ophthalmol & Visual Sci Key Lab PLA, Beijing, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

inflammation; mesangial proliferative glomerulonephritis; SOCS1; STAT1; MHC class II; NF-KAPPA-B; LUPUS NEPHRITIS; IFN-GAMMA; T-CELLS; DIABETIC-NEPHROPATHY; GLOMERULAR-LESIONS; IGA NEPHROPATHY; TNF-ALPHA; CLASS-I; CRESCENTIC GLOMERULONEPHRITIS;

D O I：

10.3389/fimmu.2018.01982

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mesangial proliferative glomerulonephritis (MsGN) is a significant global threat to public health. Inflammation plays a crucial role in MsGN; however, the underlying mechanism remains unknown. Herein, we demonstrate that suppression of the cytokine signaling-1 (SOCS1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway is associated with renal inflammation and renal injury in MsGN. Using MsGN rat (Thy1.1 GN) and mouse (Habu GN) models, renal SOCS1/STAT1 was determined to be associated with CD4+ T cell infiltration and related cytokines. In vitro, SOCS1 overexpression repressed IFN-gamma-induced MHC class II and cytokine levels and STAT1 phosphorylation in mesangial cells. SOCS1 and STAT1 inhibitors significantly inhibited IFN-gamma-induced CIITA promoter activity and MHC class II expression. In conclusion, our study emphasizes the pivotal role of the SOCS1/STAT1 axis in the regulation of inflammation in MsGN.

引用

页数：14

共 60 条

[31] Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy [J].

Myllymaki, J. M. ;

Honkanen, T. T. ;

Syrjanen, J. T. ;

Helin, H. J. ;

Rantala, I. S. ;

Pasternack, A. I. ;

Mustonen, J. T. .

KIDNEY INTERNATIONAL, 2007, 71 (04) :343-348

[32]

Nakao N, 1998, AM J PATHOL, V152, P1237

[33] Interleukin 12 induces crescentic glomerular lesions in a high IgA strain of ddY mice, independently of changes in IgA deposition [J].

Nogaki, F ;

Muso, E ;

Kobayashi, I ;

Kusano, H ;

Shirakawa, K ;

Kamata, T ;

Oyama, A ;

Ono, T ;

Miyawaki, S ;

Yoshida, M ;

Sasayama, S .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2000, 15 (08) :1146-1154

[34] IFN-γ regulation of class II transactivator promoter IV in macrophages and microglia:: Involvement of the suppressors of cytokine signaling-1 protein [J].

O'Keefe, GM ;

Nguyen, VT ;

Tang, LP ;

Benveniste, EN .

JOURNAL OF IMMUNOLOGY, 2001, 166 (04) :2260-2269

[35] Kidney-infiltrating CD4+ T-cell clones promote nephritis in lupus-prone mice [J].

Okamoto, Akiko ;

Fujio, Keishi ;

Tsuno, Nelson H. ;

Takahashi, Koki ;

Yamamoto, Kazuhiko .

KIDNEY INTERNATIONAL, 2012, 82 (09) :969-979

[36] Suppressors of Cytokine Signaling Abrogate Diabetic Nephropathy [J].

Ortiz-Munoz, Guadalupe ;

Lopez-Parra, Virginia ;

Lopez-Franco, Oscar ;

Fernandez-Vizarra, Paula ;

Mallavia, Benat ;

Flores, Claudio ;

Sanz, Ana ;

Blanco, Julia ;

Mezzano, Sergio ;

Ortiz, Alberto ;

Egido, Jesus ;

Gomez-Guerrero, Carmen .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2010, 21 (05) :763-772

[37] 15-Deoxy-Δ12,14-prostaglandin J2 inhibits INF-γ-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells [J].

Panzer, Ulf ;

Zahner, Gunther ;

Wienberg, Ulrike ;

Steinmetz, Oliver M. ;

Peters, Anett ;

Turner, Jan-Eric ;

Paust, Hans-Joachim ;

Wolf, Gunter ;

Stahl, Rolf A. K. ;

Schneider, Andre .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2008, 23 (12) :3776-3785

[38] Renal Interstitial Infiltration and Tertiary Lymphoid Organ Neogenesis in IgA Nephropathy [J].

Pei, Guangchang ;

Zeng, Rui ;

Han, Min ;

Liao, Panli ;

Zhou, Xuan ;

Li, Yueqiang ;

Zhang, Ying ;

Liu, Ping ;

Zhang, Chunxiu ;

Liu, XiaoCheng ;

Yao, Ying ;

Xu, Gang .

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2014, 9 (02) :255-264

[39] Decreased SOCS1 mRNA expression levels in peripheral blood mononuclear cells from patients with systemic lupus erythematosus in a Chinese population [J].

Qiu, Li-Juan ;

Xu, Ke ;

Liang, Yan ;

Cen, Han ;

Zhang, Min ;

Wen, Peng-Fei ;

Ni, Jing ;

Xu, Wang-Dong ;

Leng, Rui-Xue ;

Pan, Hai-Feng ;

Ye, Dong-Qing .

CLINICAL AND EXPERIMENTAL MEDICINE, 2015, 15 (03) :261-267

[40] Suppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic Nephropathy [J].

Recio, Carlota ;

Lazaro, Iolanda ;

Oguiza, Ainhoa ;

Lopez-Sanz, Laura ;

Bernal, Susana ;

Blanco, Julia ;

Egido, Jesus ;

Gomez-Guerrero, Carmen .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (02) :575-585

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