Nexilin Regulates Oligodendrocyte Progenitor Cell Migration and Remyelination and Is Negatively Regulated by Protease-Activated Receptor 1/Ras-Proximate-1 Signaling Following Subarachnoid Hemorrhage

Overview

Journal Front Neurol

Specialty Neurology

Date 2018 Jun 21

PMID 29922213

Citations 12

Authors

Qiang Li

Hengli Zhao

Pengyu Pan

Xufang Ru

Shilun Zuo

Jie Qu

Bin Liao

Yujie Chen

Huaizhen Ruan

Hua Feng

Affiliations

Soon will be listed here.

Abstract

Progressive white matter (WM) impairments caused by subarachnoid hemorrhage (SAH) contribute to cognitive deficits and poor clinical prognoses; however, their pathogenetic mechanisms are poorly understood. We investigated the role of nexilin and oligodendrocyte progenitor cell (OPC)-mediated repair in a mouse model of experimental SAH generated left endovascular perforation. Nexilin expression was enhanced by the elevated migration of OPCs after SAH. Knocking down nexilin by siRNA reduced OPC migration both and and abridged WM repair. In contrast, the protease-activated receptor 1 (PAR1), Ras-proximate-1 (RAP1) and phosphorylated RAP1 (pRAP1) levels in WM were elevated after SAH. The genetic inhibition of PAR1 reduced RAP1 and pRAP1 expression, further enhancing nexilin expression. When delivered at an early stage at a concentration of 25 µg/kg, thrombin receptor antagonist peptide along with PAR1 knockdown rescued the down-regulation of myelin basic protein and improved remyelination at the later stage of SAH. Our results suggest that nexilin is required for OPC migration and remyelination following SAH, as it negatively regulates PAR1/RAP1 signaling, thus providing a promising therapeutic target in WM repair and functional recovery.

Citing Articles

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