Janus Kinase 2/Signal Transducers and Activators of Transcription Signal Inhibition Regulates Protective Effects of Probucol on Mesangial Cells Treated with High Glucose

被引:26
作者
Du, Juan [1 ,2 ]
Wang, Lining [1 ]
Liu, Xiaodan [1 ]
Zhou, Hongli [1 ]
Fan, Qiuling [1 ]
Luo, Jialin [2 ]
Yao, Li [1 ]
Wang, Jun [1 ]
Feng, Jiangmin [1 ]
Ma, Jianfei [1 ]
机构
[1] China Med Univ, Hosp 1, Dept Nephrol, Shenyang 110001, Peoples R China
[2] Daqing Oilfield Gen Hosp, Dept Nephrol, Daqing 163000, Peoples R China
关键词
mesangial cell; probucol; Janus kinase 2; ANTIOXIDANT PROBUCOL; PATHWAY; MUSCLE; EXPRESSION; INDUCTION;
D O I
10.1248/bpb.33.768
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Probucol is a cholesterol-lowering drug with an anti-proliferative effect. Excessive growth of glomerular mesangial cells and overexpression of transforming growth factor-beta 1 (TGF-beta 1) and connective tissue growth factor (CTGF) are the pathological features of diabetic nephropathy. In this study, human mesangial cells (HMCs) treated with high glucose showed the above-mentioned features through the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT) pathway. Probucol can suppress cell proliferation, down-regulate mRNA and protein levels of TGF-beta 1 and CTGF in HMCs treated with high glucose. Phosphorylation of JAK2, STAT1 and STAT3 caused by high glucose was obviously prevented in HMCs pretreated with probucol, indicating that the protective effect of probucol on HMCs might be through the inhibition of JAK2/STAT pathway. Therefore, probucol could be a potential therapeutic agent for diabetic nephropathy, and this paper provides new insights into the molecular mechanisms underlying probucol's effects.
引用
收藏
页码:768 / 772
页数:5
相关论文
共 26 条
[1]   Expression, Localization, and Function of the Thioredoxin System in Diabetic Nephropathy [J].
Advani, Andrew ;
Gilbert, Richard E. ;
Thai, Kerri ;
Gow, Renae M. ;
Langham, Robyn G. ;
Cox, Alison J. ;
Connelly, Kim A. ;
Zhang, Yuan ;
Herzenberg, Andrew M. ;
Christensen, Per Knud ;
Pollock, Carol A. ;
Qi, Weier ;
Tan, Sih Min ;
Parving, Hans-Henrik ;
Kelly, Darren J. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (04) :730-741
[2]   Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells [J].
Amiri, F ;
Venema, VJ ;
Wang, XD ;
Ju, H ;
Venema, RC ;
Marrero, MB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (45) :32382-32386
[3]   Regulation of angiotensin II receptors and PKC isoforms by glucose in rat mesangial cells [J].
Amiri, F ;
Garcia, R .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1999, 276 (05) :F691-F699
[4]   Angiotensin II activation of the JAK/STAT pathway in mesangial cells is altered by high glucose [J].
Amiri, F ;
Shaw, S ;
Wang, XD ;
Tang, J ;
Waller, JL ;
Eaton, DC ;
Marrero, MB .
KIDNEY INTERNATIONAL, 2002, 61 (05) :1605-1616
[5]   Identification of human ccn2*(connective tissue growth factor) promoter polymorphisms [J].
Blom, IE ;
van Dijk, AJ ;
de Weger, RA ;
Tilanus, MGJ ;
Goldschmeding, R .
JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY, 2001, 54 (03) :192-196
[6]   Induction of adiponectin in skeletal muscle of type 2 diabetic mice: in vivo and in vitro studies [J].
Delaigle, AM ;
Senou, M ;
Guiot, Y ;
Many, MC ;
Brichard, SM .
DIABETOLOGIA, 2006, 49 (06) :1311-1323
[7]   The mitogen-activated protein kinase Erk5 mediates human mesangial cell activation [J].
Dorado, Fernando ;
Velasco, Soraya ;
Esparis-Ogando, Azucena ;
Pericacho, Miguel ;
Pandiella, Atanasio ;
Silva, Juan ;
Lopez-Novoa, Jose M. ;
Rodriguez-Barbero, Alicia .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2008, 23 (11) :3403-3411
[8]   Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose [J].
Ha, HJ ;
Lee, HB .
KIDNEY INTERNATIONAL, 2000, 58 :S19-S25
[9]   Suppressors of cytokine signaling regulate angiotensin II-activated janus kinase-signal transducers and activators of transcription pathway in renal cells [J].
Hernández-Vargas, P ;
López-Franco, O ;
Sanjuán, G ;
Rupérez, M ;
Ortiz-Muñoz, G ;
Suzuki, Y ;
Aguado-Roncero, P ;
Pérez-Tejerizo, G ;
Blanco, J ;
Egido, J ;
Ruiz-Ortega, M ;
Gómez-Guerrero, C .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (06) :1673-1683
[10]   Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells [J].
Huang, JS ;
Guh, JY ;
Hung, WC ;
Yang, ML ;
Lai, YH ;
Chen, HC ;
Chuang, LY .
BIOCHEMICAL JOURNAL, 1999, 342 :231-238