Abstract：
:Hypoxic blood-brain barrier (BBB) dysfunction is a common feature of CNS diseases however mechanisms underlying barrier disturbance are still largely unknown. This study investigated the role of transforming growth factor β (TGFβ), a cytokine known to induce expression of the proprotein convertase Furin, in hypoxia-mediated barrier compromise. We show that exposure of brain endothelial cells (ECs) to hypoxia (1% O2) rapidly stimulates their migration. Additional exogenous TGFβ (0.4 nM) exposure potentiated this effect and increased Furin expression in a TGFβ type I receptor activin-like kinase 5 (ALK5) - dependent manner (prevented by 10 μM SB431542). Furin inhibition prevented hypoxia-induced EC migration and blocked TGFβ-induced potentiation suggesting existence of a feedback loop. TGFβ and Furin were also critical for hypoxia-induced BBB dysfunction. TGFβ treatment aggravated hypoxia-induced BBB permeability but ALK5 or Furin blockade reversed injury-induced permeability changes. Thus during insult Furin compromises endothelial integrity by mediating the effects of TGFβ. Targeting the Furin or ALK5 pathway may offer novel therapeutic strategies for improving BBB stability and CNS function during disease.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Baumann J,Huang SF,Gassmann M,Tsao CC,Ogunshola OOdoi
10.1016/j.yexcr.2019.111503subject
Has Abstractpub_date
2019-10-15 00:00:00pages
111503issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(19)30344-1journal_volume
383pub_type
杂志文章abstract：:In primary cultures of ovine thyroid cells, TSH induced the expression of several differentiated functions including the formation of follicles, and synthesis and storage of iodinated thyroglobulin in the follicular lumen. In the present report, these follicles were shown by transmission (TEM) and scanning electron mi...
journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
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journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
pub_type： 杂志文章
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更新日期：2005-10-15 00:00:00
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pub_type： 杂志文章
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更新日期：2004-07-15 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2016.02.014
更新日期：2016-03-01 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
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更新日期：2020-12-22 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1993.1142
更新日期：1993-06-01 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/s0014-4827(83)80023-8
更新日期：1983-04-15 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2005.12.022
更新日期：2006-05-01 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2005.06.024
更新日期：2005-10-01 00:00:00
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journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
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journal_title：Experimental cell research
pub_type： 杂志文章
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更新日期：2011-08-01 00:00:00
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journal_title：Experimental cell research
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journal_title：Experimental cell research
pub_type： 杂志文章
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更新日期：2004-07-01 00:00:00
abstract：:Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis....
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pub_type： 杂志文章
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更新日期：2018-01-01 00:00:00
abstract：:Small vertebrate organisms have emerged as key players in the post-genomic era for the functional characterization of novel genes on a high-throughput scale. In this context, the zebrafish embryos and Xenopus tadpoles represent attractive and valuable models to rapidly identify and characterize novel genes involved in...
journal_title：Experimental cell research
pub_type： 杂志文章,评审
doi：10.1016/j.yexcr.2005.10.018
更新日期：2006-03-10 00:00:00
abstract：:Regulatory B cells (Breg cells) play critical roles in modulating immune responses during autoimmune diseases and infection. Here we explored the participation of two main Breg subsets, including IL-10+ Breg (B10) and IL-35+ Breg cells, in maintaining successful pregnancy. We first observed an elevated percentage of B...
journal_title：Experimental cell research
pub_type： 杂志文章
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abstract：:Protein kinase B (Akt1) holds a central role for cellular growth, development, and survival, but the cellular pathways of Akt1 that prevent inflammatory demise in the vascular system remain undefined. Employing a constitutively active form of Akt1 (myristoylated Akt1) in endothelial cells (ECs), we demonstrate that Ak...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1016/j.yexcr.2004.01.021
更新日期：2004-06-10 00:00:00
abstract：:Over-activation of beta-catenin/TCF signaling has been frequently observed in hepatocellular carcinoma (HCC). Better understanding the molecular mechanism for the aberrant activation of beta-catenin/TCF signaling would provide novel insights into the treatment of this malignancy. In this study, we have shown that the ...
journal_title：Experimental cell research
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更新日期：2017-09-15 00:00:00
