File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1016/j.neuroscience.2020.09.031
- Scopus: eid_2-s2.0-85092534447
- PMID: 32976986
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Caveolin-1 Derived from Brain Microvascular Endothelial Cells Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells In Vivo and In Vitro
Title | Caveolin-1 Derived from Brain Microvascular Endothelial Cells Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells In Vivo and In Vitro |
---|---|
Authors | |
Keywords | brain microvascular endothelial cells caveolin-1 neural progenitor cells neurogenesis stroke |
Issue Date | 2020 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience |
Citation | Neuroscience, 2020, v. 448, p. 172-190 How to Cite? |
Abstract | Caveolin-1 (Cav-1) is an important modulator for adult neurogenesis in post stroke brain repair but its underlying mechanisms are largely unknown. In the present study, we report that endothelial Cav-1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) in post ischemic brain via regulating vascular endothelial growth factor (VEGF) and NeuroD1 signaling pathway. We first investigated the dynamic change of Cav-1 and its impact on neuronal differentiation in rat and mouse models of 2 h transient middle cerebral artery occlusion (MCAO) plus 1, 7, 14, 21 and 28 day of reperfusion. We then studied the roles of endothelial Cav-1 in modulating the neuronal differentiation of NPCs which were co-cultured with brain microvascular endothelial cells (BMVECs) under 2 h oxygen-glucose deprivation plus 5 days reoxygenation (OGD/R). The major discoveries include: (1) Cav-1 expression in the hippocampal dentate gyrus (DG) was down-regulated on day 1 after 2 h cerebral ischemia, and gradually recovered with reperfusion time, accompanied with transient increased but gradually reduced neuronal differentiation of NPCs marked by doublecortin (DCX). (2) Cav-1 knockout mice exhibited the increased DCX and VEGF at the granular cell layers of hippocampal DG in post-ischemic brains. (3) Co-cultured with BMVECs, NPCs had remarkably decreased neuronal differentiation under OGD/R. Knockdown of Cav-1 in the BMVECs increased VEGF secretion into the medium and NeuroD1+ cells, and rescued the neuronal differentiation of NPCs without affecting astroglial and oligodendroglial differentiation. (4) Cav-1 exosomes released from BMVECs inhibited neuronal differentiation of NPCs via decreasing the expression of VEGF, p44/42MAPK phosphorylation and NeuronD1 upon OGD/R insults. Taken together, endothelial Cav-1 serves as a niche regulator to inhibit neuronal differentiation via negatively modulating VEGF, p44/42MAPK phosphorylation and NeuronD1 signaling pathway. |
Persistent Identifier | http://hdl.handle.net/10722/290504 |
ISSN | 2023 Impact Factor: 2.9 2023 SCImago Journal Rankings: 0.903 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Li, Y | - |
dc.contributor.author | Zhao, Y | - |
dc.contributor.author | Gao, C | - |
dc.contributor.author | WU, M | - |
dc.contributor.author | So, KF | - |
dc.contributor.author | Tong, Y | - |
dc.contributor.author | Shen, J | - |
dc.date.accessioned | 2020-11-02T05:43:11Z | - |
dc.date.available | 2020-11-02T05:43:11Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Neuroscience, 2020, v. 448, p. 172-190 | - |
dc.identifier.issn | 0306-4522 | - |
dc.identifier.uri | http://hdl.handle.net/10722/290504 | - |
dc.description.abstract | Caveolin-1 (Cav-1) is an important modulator for adult neurogenesis in post stroke brain repair but its underlying mechanisms are largely unknown. In the present study, we report that endothelial Cav-1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) in post ischemic brain via regulating vascular endothelial growth factor (VEGF) and NeuroD1 signaling pathway. We first investigated the dynamic change of Cav-1 and its impact on neuronal differentiation in rat and mouse models of 2 h transient middle cerebral artery occlusion (MCAO) plus 1, 7, 14, 21 and 28 day of reperfusion. We then studied the roles of endothelial Cav-1 in modulating the neuronal differentiation of NPCs which were co-cultured with brain microvascular endothelial cells (BMVECs) under 2 h oxygen-glucose deprivation plus 5 days reoxygenation (OGD/R). The major discoveries include: (1) Cav-1 expression in the hippocampal dentate gyrus (DG) was down-regulated on day 1 after 2 h cerebral ischemia, and gradually recovered with reperfusion time, accompanied with transient increased but gradually reduced neuronal differentiation of NPCs marked by doublecortin (DCX). (2) Cav-1 knockout mice exhibited the increased DCX and VEGF at the granular cell layers of hippocampal DG in post-ischemic brains. (3) Co-cultured with BMVECs, NPCs had remarkably decreased neuronal differentiation under OGD/R. Knockdown of Cav-1 in the BMVECs increased VEGF secretion into the medium and NeuroD1+ cells, and rescued the neuronal differentiation of NPCs without affecting astroglial and oligodendroglial differentiation. (4) Cav-1 exosomes released from BMVECs inhibited neuronal differentiation of NPCs via decreasing the expression of VEGF, p44/42MAPK phosphorylation and NeuronD1 upon OGD/R insults. Taken together, endothelial Cav-1 serves as a niche regulator to inhibit neuronal differentiation via negatively modulating VEGF, p44/42MAPK phosphorylation and NeuronD1 signaling pathway. | - |
dc.language | eng | - |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience | - |
dc.relation.ispartof | Neuroscience | - |
dc.subject | brain microvascular endothelial cells | - |
dc.subject | caveolin-1 | - |
dc.subject | neural progenitor cells | - |
dc.subject | neurogenesis | - |
dc.subject | stroke | - |
dc.title | Caveolin-1 Derived from Brain Microvascular Endothelial Cells Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells In Vivo and In Vitro | - |
dc.type | Article | - |
dc.identifier.email | Gao, C: colingao@hku.hk | - |
dc.identifier.email | So, KF: hrmaskf@hku.hk | - |
dc.identifier.email | Tong, Y: tongyao@hku.hk | - |
dc.identifier.email | Shen, J: shenjg@hku.hk | - |
dc.identifier.authority | So, KF=rp00329 | - |
dc.identifier.authority | Tong, Y=rp00509 | - |
dc.identifier.authority | Shen, J=rp00487 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.neuroscience.2020.09.031 | - |
dc.identifier.pmid | 32976986 | - |
dc.identifier.scopus | eid_2-s2.0-85092534447 | - |
dc.identifier.hkuros | 317964 | - |
dc.identifier.volume | 448 | - |
dc.identifier.spage | 172 | - |
dc.identifier.epage | 190 | - |
dc.publisher.place | Netherlands | - |
dc.identifier.issnl | 0306-4522 | - |