TIMP1 protects against blood-brain barrier disruption after subarachnoid haemorrhage by inhibiting ubiquitination of astrocytic β1-integrin.

ABSTRACT:

Background

Astrocytes regulate blood-brain barrier (BBB) integrity, whereas subarachnoid haemorrhage (SAH) results in astrocyte dysregulation and BBB disruption. Here, we explored the involvement of tissue inhibitor of matrix metalloprotease-1 (TIMP1) in astrocyte-mediated BBB protection during SAH, along with its underlying mechanisms.

Methods

C57BL/6J mice were used to establish a model of SAH. The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein (rm-TIMP1; 250 µg/kg). The roles of TIMP1 and its effector β1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid or β1-integrin RNAi. The molecular mechanisms underlying TIMP1

SUBMITTER: Tang T 

PROVIDER: S-EPMC11791639 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature