First Author | Jin Z | Year | 2019 |
Journal | Int J Mol Sci | Volume | 20 |
Issue | 13 | PubMed ID | 31261992 |
Mgi Jnum | J:289893 | Mgi Id | MGI:6435086 |
Doi | 10.3390/ijms20133214 | Citation | Jin Z, et al. (2019) Absence of MCP-induced Protein 1 Enhances Blood-Brain Barrier Breakdown after Experimental Stroke in Mice. Int J Mol Sci 20(13):3214 |
abstractText | Focal cerebral ischemia can cause blood-brain barrier (BBB) breakdown, which is implicated in neuroinflammation and progression of brain damage. Monocyte chemotactic protein 1-induced protein 1 (MCPIP1) is a newly identified zinc-finger protein that negatively regulates inflammatory signaling pathways. We aimed to evaluate the impact of genetic MCPIP1 deletion on BBB breakdown and expression of BBB-related matrix metalloproteinases (MMPs) and tight junction proteins after cerebral ischemia/reperfusion (I/R) using MCPIP1-deficient (MCPIP1(-/-)) mice. Transient middle cerebral artery occlusion was induced in the MCPIP1(-/-) mice and their wild-type littermates for 2 h followed by reperfusion for 24 h. The degree of BBB breakdown was evaluated by injection of fluorescein isothiocyanate (FITC)-dextran. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were performed to compare the expression of MMPs and claudin-5 and zonula occludens-1 (ZO-1). MCPIP1 deficiency in mice resulted in enhanced leakage of FITC-dextran, increased expression of MMP-9/3, and reduced expression of claudin-5 and ZO-1 in the brain compared to that seen in their wild-type littermates subjected to cerebral I/R. These results demonstrate that absence of MCPIP1 exacerbates cerebral I/R-induced BBB disruption by enhancing the expression of MMP-9/3 and the degradation of claudin-5 and ZO-1, providing novel insights into the mechanisms underlying BBB breakdown after cerebral ischemia/reperfusion. |