Research on MMP-9 to promote mesenchymal stem cells migration through the blood-brain barrier
10.3760/cma.j.issn.1673-4181.2014.01.002
- VernacularTitle:MMP-9促进间充质干细胞穿越血脑屏障的作用研究
- Author:
Liping ZHOU
;
Qin YU
;
Jie LIN
;
Shaojun HU
- Publication Type:Journal Article
- Keywords:
Mesenchymal stem cells;
Matrix metalloproteinases-9;
Hypoxia-ischemia;
Blood-brain barrier
- From:
International Journal of Biomedical Engineering
2014;37(1):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of MMP-9 in blood-brain barrier (BBB) disruption and to promote rMSCs migration.Methods To investigate the effect of MMP-9 on the permeability of BBB,an in vitro model of BBB was established and performed Transwell experiments.To observe the pathologic changes of the cerebral cortex,rat brains from Sham treated group,HIBD group,MMP-9 treated group and TIMP-1 (intervention) treated group at different time points (0.5,1,3,7,14 d) were prepared and stained with Hematoxylin-Eosin and quantified the brain water content.Permeability of BBB examined by EB values measurement.MMP-9 protein level of rat cortex was detected by Western Blot.The number of Brdu labeled rMSCs in the rat cerebral cortex of each group was quantified by Immunohistochemistry (IHC).Results Transwell experiments results showed that migration of rMSCs increased remarkably in hypoxic condition compared to that of normal control (P＜0.01).The number of rMSCs migrated in the MMP-9 treated group was much more than that of negative control group and TIMP-1 group (P＜0.01).The results of pathology showed that compared to HIBD group,brain water content and the permeability of the BBB were increased in MMP-9 treated group but reduced in TIMP-1 treated one.The expression of MMP-9 protein in MMP-9 treated group was reached the peak at 3 d point,which was higher than that of HIBD group and TIMP-1 group (P＜0.05,P＜0.01).The quantity of Brdu labeled rMSCs crossed BBB in MMP-9 treated group was extremely higher than that of HIBD group (P＜0.05,P＜0.01).Conclusions The expression level of MMp-9 protein was improved after hypoxic-ischemic.MMP-9 could facilitate the migration of rMSCs through vitro BBB and control the opening of BBB,which indicate that MMP-9 may facilitate the migration of rMSCs through BBB into brain.
