p38 MAPK pathway is involved in high glucose-induced thioredoxin interacting protein induction in mouse mesangial cells.
Excessive reactive oxygen species (ROS) play a key role in the pathogenesis of diabetic nephropathy. The thioredoxin (TRX) system, a major thiol antioxidant system, regulates the reduction of intracellular ROS. Here we show that high glucose (HG) inhibits TRX ROS-scavenging function through p38 mitogen-activated protein kinase (MAPK)-mediated induction of thioredoxin interacting protein (TXNIP) in mouse mesangial cells (MMCs). Knockdown of TXNIP in MMCs reversed HG-induced reduction of TRX activity and inhibited HG-induced activation of p38 MAPK and increased synthesis of TGF-beta1 and fibronectin. These data suggest that HG-induced overexpression of TXNIP in MMCs, which may be via the p38 MAPK pathway.
Ren
Yunzhuo
Y
Department of Pathology, Hebei Medical University, and Department of Nephrology, Third Hospital, No. 361 East Zhongshan Road, Shijiazhuang 050017, China.
Shi
Yonghong
Y
Wang
Yuehua
Y
Li
Yingmin
Y
Wu
Shuhui
S
Li
Hang
H
Zhang
Yanling
Y
Duan
Huijun
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D034622:RNA Interference / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002352:Carrier Proteins; D005353:Fibronectins; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; C445672:Txnip protein, mouse; D013879:Thioredoxins; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose