Serine Protease Inhibitor A3K Protects Rabbit Corneal Endothelium From Barrier Function Disruption Induced by TNF-alpha

CORC > 厦门大学 > 医学院－已发表论文

	Serine Protease Inhibitor A3K Protects Rabbit Corneal Endothelium From Barrier Function Disruption Induced by TNF-alpha
	Hu, Jiaoyue ; Zhang, Zhenhao ; Xie, Hui ; Chen, Lelei ; Zhou, Yueping ; Chen, Wensheng ; Liu, Zuguo ; Hu JY(胡皎月) ; Zhou YP(周跃平) ; Chen WS(陈文生) ; Liu ZG(刘祖国)
刊名	http://dx.doi.org/10.1167/iovs.12-10145
	2013
关键词	NECROSIS-FACTOR-ALPHA KALLIKREIN-BINDING PROTEIN EPITHELIAL-CELLS TIGHT JUNCTIONS GROWTH-FACTOR KAPPA-B MECHANISMS SERPINA3K INTEGRITY UVEITIS
英文摘要	National Basic Research Program of China (Project 973) [2011CB504606]; National Natural Science Foundation of China (Beijing, China) [81100638, 30973249]; Science and Technology Project of Xiamen [3502Z20124039]; PURPOSE. To determine if a serine protease inhibitor A3K (SA3K) reduces TNF-alpha-induced declines in rabbit corneal endothelial junctional barrier integrity. METHODS. New Zealand rabbit corneas were incubated ex vivo for 24 hours in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS with or without TNF-alpha, in the presence or absence of SA3K at different concentrations. Corneal endothelial barrier function permeability was determined based on measurements of FITC-dextran tissue accumulation. Apical junctional complex (AJC) integrity was evaluated of zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, and filamentous actin (F-actin) and associated microtubules, as well as myosin light chain (MLC) by immunofluorescent staining, Western blot analysis, and/or RT-PCR. RESULTS. TNF-alpha (20 ng/mL) increased corneal endothelial FITC-dextran permeability by 1.8-fold compared with the untreated control. SA3K (100-200 nM) dose dependently suppressed TNF-alpha-induced increases in permeability. SA3K nearly completely reversed TNF-alpha-induced disruptions of tight junctional ZO-1 and subjacent adherens junctions VE-cadherin integrity. Interestingly, SA3K reversed TNF-alpha-induced disruption of AJC linkage to the cytoskeletal F-actin array by restoring F-actin double-band structures. SA3K also attenuated TNF-alpha-induced microtubule disassembly. Furthermore, SA3K blocked increases in MLC phosphorylation status elicited by TNF-alpha. CONCLUSIONS. SA3K exposure markedly reduced TNF-alpha-induced disruption of barrier structure and function in the rabbit corneal endothelium by maintaining AJC integrity. These protective effects are due to suppression of MLC activation. SA3K may have, in vivo, a therapeutic potential to offset TNF-alpha-induced declines in endothelial barrier structural integrity and function.
语种	英语
出版者	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93509]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Hu, Jiaoyue,Zhang, Zhenhao,Xie, Hui,et al. Serine Protease Inhibitor A3K Protects Rabbit Corneal Endothelium From Barrier Function Disruption Induced by TNF-alpha[J]. http://dx.doi.org/10.1167/iovs.12-10145,2013.
APA	Hu, Jiaoyue.,Zhang, Zhenhao.,Xie, Hui.,Chen, Lelei.,Zhou, Yueping.,...&刘祖国.(2013).Serine Protease Inhibitor A3K Protects Rabbit Corneal Endothelium From Barrier Function Disruption Induced by TNF-alpha.http://dx.doi.org/10.1167/iovs.12-10145.
MLA	Hu, Jiaoyue,et al."Serine Protease Inhibitor A3K Protects Rabbit Corneal Endothelium From Barrier Function Disruption Induced by TNF-alpha".http://dx.doi.org/10.1167/iovs.12-10145 (2013).