Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity.

Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity.
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间接接触共培养的周细胞通过升级 MMP-2/9 活性降低体外内血视网膜屏障模型的完整性

DOI:
10.1155/2021/7124835
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发表时间:
2021
期刊:
影响因子:
--
通讯作者:
Liu G
Liu G
中科院分区:
医学4区
文献类型:
--
作者:
Yang T;Guo L;Fang Y;Liang M;Zheng Y;Pan M;Meng C;Liu G

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Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction.
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