Premium
Macrophage stimulating protein preserves blood brain barrier integrity after intracerebral hemorrhage through recepteur d'origine nantais dependent GAB1/Src/β‐catenin pathway activation in a mouse model
Author(s) -
Lu Tai,
Wang Zhong,
Prativa Sherchan,
Xu Yang,
Wang Tian,
Zhang Yiting,
Yu Lingyan,
Xu Ningbo,
Tang Jiping,
You Wanchun,
Chen Gang,
Zhang John H.
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14622
Subject(s) - blood–brain barrier , tight junction , proto oncogene tyrosine protein kinase src , signal transduction , microbiology and biotechnology , cancer research , evans blue , chemistry , biology , endocrinology , central nervous system
Blood brain barrier (BBB) disruption is an important contributor to brain edema and neurological deficits following intracerebral hemorrhage (ICH). Macrophage stimulating protein (MSP) is a hepatocyte growth factor‐like protein that mediates its functions via activating receptor tyrosine kinase recepteur d'origine nantais (RON). Grb2‐associated binder 1 (GAB1) is a docking protein that mediates downstream receptor signal transduction pathways. This study aimed to evaluate the role of MSP and RON activated signaling pathway in preserving BBB integrity after collagenase‐induced ICH. ICH mice received recombinant human MSP (rhMSP) or rhMSP combined with siRNA knockdown of RON or GAB1. rhMSP was administered by intranasal route 1 h after ICH. Brain edema, neurobehavior, BBB tight junction protein expression, and BBB permeability were evaluated. The expression of endogenous MSP and p‐RON was decreased after ICH. Exogenous rhMSP administration reduced brain edema, neurological deficits, BBB permeability, and increased the expression of tight junction proteins in ICH mice. rhMSP administration increased the expression of p‐RON, p‐GAB1, p‐Src, nuclear β‐catenin, and tight junction proteins after ICH. These effects were reversed with RON and GAB1 siRNA. We conclude that MSP activation of RON preserved BBB integrity via GAB‐1/Src/β‐catenin pathway, thereby reducing brain edema and neurological deficits after ICH in mice.