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Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis.
Shun-Min Yang
1 ,
Shuk-Man Ka ,
Hua-Lin Wu ,
Yu-Chuan Yeh ,
Cheng-Hsiang Kuo ,
Kuo-Feng Hua ,
Guey-Yueh Shi ,
Yi-Jen Hung ,
Fone-Ching Hsiao ,
Sung-Sen Yang ,
Yi-Shing Shieh ,
Shih-Hua Lin ,
Chyou-Wei Wei ,
Jeng-Shin Lee ,
Chu-Yi Yang ,
Ann Chen
Feb 2014
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Abstract
Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1) were tested in a mouse model of type 2 diabetic nephropathy.