Cargando…

Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells

The blood–brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood–brain barrier (BBB...

Descripción completa

Detalles Bibliográficos
Autores principales: Fu, Jiyang, Li, Liang, Huo, Dong, Zhi, Shuli, Yang, Ruicheng, Yang, Bo, Xu, Bojie, Zhang, Tao, Dai, Menghong, Tan, Chen, Chen, Huanchun, Wang, Xiangru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826596/
https://www.ncbi.nlm.nih.gov/pubmed/33430164
http://dx.doi.org/10.3390/brainsci11010077
_version_ 1783640558268317696
author Fu, Jiyang
Li, Liang
Huo, Dong
Zhi, Shuli
Yang, Ruicheng
Yang, Bo
Xu, Bojie
Zhang, Tao
Dai, Menghong
Tan, Chen
Chen, Huanchun
Wang, Xiangru
author_facet Fu, Jiyang
Li, Liang
Huo, Dong
Zhi, Shuli
Yang, Ruicheng
Yang, Bo
Xu, Bojie
Zhang, Tao
Dai, Menghong
Tan, Chen
Chen, Huanchun
Wang, Xiangru
author_sort Fu, Jiyang
collection PubMed
description The blood–brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood–brain barrier (BBB) function. Here, we demonstrate the astrocyte-derived TGFβ1-mediated intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). By using an in vitro co-culture model, we observed that the astrocyte-derived TGFβ1 enhanced the tight junction protein ZO-1 expression in BMECs and the endothelial barrier function via a non-canonical hedgehog signaling. Gli2, the core transcriptional factor of the hedgehog pathway, was demonstrated to modulate ZO-1 expression directly. By the dual-luciferase reporter system and chromatin immunoprecipitation, we further identified the exact sites on Smad2/3 that bound to the gli2 promotor and on Gli2 that bound to the zo-1 promotor. Our work highlighted the TGFβ1-mediated intercellular communication of astrocytes with BMECs in BBB, which shall extend current knowledge on the BBB homeostasis physiologically, and more importantly suggests TGFβ1 as a potential effector for future prevention and amelioration of BBB dysfunction.
format Online
Article
Text
id pubmed-7826596
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78265962021-01-25 Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells Fu, Jiyang Li, Liang Huo, Dong Zhi, Shuli Yang, Ruicheng Yang, Bo Xu, Bojie Zhang, Tao Dai, Menghong Tan, Chen Chen, Huanchun Wang, Xiangru Brain Sci Article The blood–brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood–brain barrier (BBB) function. Here, we demonstrate the astrocyte-derived TGFβ1-mediated intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). By using an in vitro co-culture model, we observed that the astrocyte-derived TGFβ1 enhanced the tight junction protein ZO-1 expression in BMECs and the endothelial barrier function via a non-canonical hedgehog signaling. Gli2, the core transcriptional factor of the hedgehog pathway, was demonstrated to modulate ZO-1 expression directly. By the dual-luciferase reporter system and chromatin immunoprecipitation, we further identified the exact sites on Smad2/3 that bound to the gli2 promotor and on Gli2 that bound to the zo-1 promotor. Our work highlighted the TGFβ1-mediated intercellular communication of astrocytes with BMECs in BBB, which shall extend current knowledge on the BBB homeostasis physiologically, and more importantly suggests TGFβ1 as a potential effector for future prevention and amelioration of BBB dysfunction. MDPI 2021-01-08 /pmc/articles/PMC7826596/ /pubmed/33430164 http://dx.doi.org/10.3390/brainsci11010077 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fu, Jiyang
Li, Liang
Huo, Dong
Zhi, Shuli
Yang, Ruicheng
Yang, Bo
Xu, Bojie
Zhang, Tao
Dai, Menghong
Tan, Chen
Chen, Huanchun
Wang, Xiangru
Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title_full Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title_fullStr Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title_full_unstemmed Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title_short Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells
title_sort astrocyte-derived tgfβ1 facilitates blood–brain barrier function via non-canonical hedgehog signaling in brain microvascular endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826596/
https://www.ncbi.nlm.nih.gov/pubmed/33430164
http://dx.doi.org/10.3390/brainsci11010077
work_keys_str_mv AT fujiyang astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT liliang astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT huodong astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT zhishuli astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT yangruicheng astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT yangbo astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT xubojie astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT zhangtao astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT daimenghong astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT tanchen astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT chenhuanchun astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells
AT wangxiangru astrocytederivedtgfb1facilitatesbloodbrainbarrierfunctionvianoncanonicalhedgehogsignalinginbrainmicrovascularendothelialcells