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Article

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

by 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2,3,4, 1,2,3,4, 1,2,3,4 and 1,2,3,4,*
1
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
2
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China
3
Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan 430070, China
4
International Research Center for Animal Disease, Ministry of Science and Technology of the People’s Republic of China, Wuhan 430070, China
*
Author to whom correspondence should be addressed.
Brain Sci. 2021, 11(1), 77; https://doi.org/10.3390/brainsci11010077
Received: 6 December 2020 / Revised: 2 January 2021 / Accepted: 6 January 2021 / Published: 8 January 2021
(This article belongs to the Section Neuroglia)
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. View Full-Text
Keywords: blood–brain barrier; TGFβ1; hedgehog signaling; Gli2; ZO-1 blood–brain barrier; TGFβ1; hedgehog signaling; Gli2; ZO-1
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MDPI and ACS Style

Fu, J.; Li, L.; Huo, D.; Zhi, S.; Yang, R.; Yang, B.; Xu, B.; Zhang, T.; Dai, M.; Tan, C.; Chen, H.; Wang, X. Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells. Brain Sci. 2021, 11, 77. https://doi.org/10.3390/brainsci11010077

AMA Style

Fu J, Li L, Huo D, Zhi S, Yang R, Yang B, Xu B, Zhang T, Dai M, Tan C, Chen H, Wang X. Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells. Brain Sciences. 2021; 11(1):77. https://doi.org/10.3390/brainsci11010077

Chicago/Turabian Style

Fu, Jiyang, Liang Li, Dong Huo, Shuli Zhi, Ruicheng Yang, Bo Yang, Bojie Xu, Tao Zhang, Menghong Dai, Chen Tan, Huanchun Chen, and Xiangru Wang. 2021. "Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells" Brain Sciences 11, no. 1: 77. https://doi.org/10.3390/brainsci11010077

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