TIMP1 preserves the blood–brain barrier through interacting with CD63/integrin 1 complex and regulating downstream FAK/RhoA signaling

• DOI: 10.1016/j.apsb.2020.02.015
• Publication Date: 2020-03-07T11:26:30Z
• Authors: Jingshu Tang; Yuying Kang; Longjian Huang; Lei Wu; Ying Peng
• Keywords: TIMP1

Blood–brain barrier (BBB) breakdown and the associated microvascular hyperpermeability are hallmark features of several neurological disorders, including traumatic brain injury (TBI). However, there is no viable therapeutic strategy to rescue BBB function. Tissue inhibitor metalloproteinase-1 (TIMP1) has been considered be beneficial for vascular integrity, but molecular mechanisms underlying functions TIMP1 remain elusive. Here, we report that executes a protective role on neuroprotective function via ameliorating disruption in mice with experimental TBI. In human microvessel endothelial cells (HBMECs) exposed hypoxia inflammation injury, recombinant (rTIMP1) treatment maintained integrity junctional proteins trans-endothelial tightness. Mechanistically, interacts CD63/integrin β1 complex activates downstream FAK signaling, leading attenuation RhoA activation F-actin depolymerization structure stabilization. Notably, these effects depend complex, instead MMP-inhibitory Together, our results identified novel MMP-independent regulating integrity. Therapeutic interventions targeting its signaling may protect following disorders.