Janus kinase 2/signal transducers and activators of transcription signal inhibition regulates protective effects of probucol on mesangial cells treated with high glucose.
Probucol is a cholesterol-lowering drug with an anti-proliferative effect. Excessive growth of glomerular mesangial cells and overexpression of transforming growth factor-beta1 (TGF-beta1) 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-beta1 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.
Du
Juan
J
Department of Nephrology, First Hospital of China Medical University, Shenyang 110001, PR China.
Wang
Lining
L
Liu
Xiaodan
X
Zhou
Hongli
H
Fan
Qiuling
Q
Luo
Jialin
J
Yao
Li
L
Wang
Jun
J
Feng
Jiangmin
J
Ma
Jianfei
J
D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D053614:Janus Kinase 2; D005947:Glucose; D011341:Probucol