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间接接触共培养的周细胞通过上调 MMP-2/9 活性降低内血视网膜屏障模型的完整性。

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

机构信息

Department of Bioengineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, China.

Lunan Pharmaceutical Group Co. Ltd., Linyi, Shandong, China.

出版信息

Dis Markers. 2021 Sep 29;2021:7124835. doi: 10.1155/2021/7124835. eCollection 2021.

DOI:10.1155/2021/7124835
PMID:34630739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8494570/
Abstract

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 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.

摘要

内血视网膜屏障（iBRB）主要由具有紧密连接的视网膜微血管内皮细胞（ECs）形成，其被视网膜微血管周细胞（RMPs）和基膜所包围和支持。周细胞被认为在 iBRB 的生理学和病理学中起着至关重要的作用。然而，其潜在的机制仍有待充分阐明。我们开发了一种基于 Transwell 系统的新型 iBRB 模型，由大鼠视网膜 ECs 和 RMPs 的原代培养物组成。我们测试了周细胞在 EC 迁移和侵袭中的作用，检查了培养物中基质金属蛋白酶-（MMP-）2/MMP-9 的表达和活性，评估了 iBRB 的 TEER 和通透性，并评估了内皮连接的 ZO-1、occludin、claudin-5 和 VE-cadherin 的表达。我们发现，与 ECs 间接接触的 RMPs 可以增加共培养物中 MMP-2 的表达，并提高 MMP-2/9 的活性，随后降低 ECs 中 TJ 蛋白 ZO-1 和 occludin 的丰度，促进 ECs 的迁移，最终降低 iBRB 的完整性。总之，我们的数据表明，RMP 与 ECs 的相对位置通过 MMP-2/9 参与了 iBRB 的完整性，这对于治疗糖尿病性视网膜病变和其他涉及 iBRB 功能障碍的视网膜疾病具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/a5d73506d524/DM2021-7124835.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/4b85b442661b/DM2021-7124835.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/b02628e85db0/DM2021-7124835.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/e35e09f829be/DM2021-7124835.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/63c9d33e3cd4/DM2021-7124835.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/723b7185b7c5/DM2021-7124835.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/a5d73506d524/DM2021-7124835.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/4b85b442661b/DM2021-7124835.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/b02628e85db0/DM2021-7124835.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/e35e09f829be/DM2021-7124835.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/63c9d33e3cd4/DM2021-7124835.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/723b7185b7c5/DM2021-7124835.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/183d/8494570/a5d73506d524/DM2021-7124835.006.jpg

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