Excess vascular endothelial growth factor-A disrupts pericyte recruitment during blood vessel formation

周细胞 血管生成 细胞生物学 壁细胞 萌芽血管生成 生物 Notch信号通路 血管内皮生长因子 血小板源性生长因子受体 生长因子 血管内皮生长因子B 血管内皮生长因子C 血管内皮生长因子A 信号转导 内皮干细胞 新生血管 受体 癌症研究 体外 遗传学 血管内皮生长因子受体
作者
Jordan Darden,Laura Beth Payne,Huaning Zhao,John C. Chappell
出处
期刊:Angiogenesis [Springer Nature]
卷期号:22 (1): 167-183 被引量:55
标识
DOI:10.1007/s10456-018-9648-z
摘要

Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations. Pericytes had little to no expression of VEGF receptors, suggesting VEGF-A signaling defects affect endothelial cells directly but pericytes indirectly. Live imaging of ex vivo angiogenesis in mouse embryonic skin revealed limited pericyte migration during exposure to exogenous VEGF-A. During VEGF-A gain-of-function conditions, pericytes and endothelial cells displayed abnormal transcriptional changes within the platelet-derived growth factor-B (PDGF-B) and Notch pathways. To further test potential crosstalk between these pathways in pericytes, we stimulated embryonic pericytes with Notch ligands Delta-like 4 (Dll4) and Jagged-1 (Jag1) and found induction of Notch pathway activity but no changes in PDGF Receptor-β (Pdgfrβ) expression. In contrast, PDGFRβ protein levels decreased with mis-regulated VEGF-A activity, observed in the effects on full-length PDGFRβ and a truncated PDGFRβ isoform generated by proteolytic cleavage or potentially by mRNA splicing. Overall, these observations support a model in which, during the initial stages of vascular development, pericyte distribution and coverage are indirectly affected by endothelial cell VEGF-A signaling and the downstream regulation of PDGF-B-PDGFRβ dynamics, without substantial involvement of pericyte Notch signaling during these early stages.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
上官若男应助呜呼咚咚采纳,获得10
2秒前
sarah完成签到,获得积分10
4秒前
WTT完成签到 ,获得积分10
5秒前
7秒前
zzf完成签到,获得积分20
7秒前
dy完成签到,获得积分10
10秒前
俭朴尔竹发布了新的文献求助10
12秒前
15秒前
Zz完成签到,获得积分20
16秒前
18秒前
19秒前
20秒前
CodeCraft应助小菜狗采纳,获得10
20秒前
20秒前
午夜时分收病人完成签到,获得积分10
24秒前
长街发布了新的文献求助20
24秒前
lucky发布了新的文献求助10
24秒前
思源应助学习采纳,获得10
25秒前
Zz发布了新的文献求助10
26秒前
27秒前
赘婿应助Taylor采纳,获得10
29秒前
不配.应助长街采纳,获得10
34秒前
36秒前
汉堡完成签到,获得积分10
36秒前
37秒前
学习发布了新的文献求助10
40秒前
41秒前
lcls发布了新的文献求助10
41秒前
orixero应助八戒的梦想采纳,获得10
42秒前
热心的寒天完成签到,获得积分10
43秒前
46秒前
加减乘除发布了新的文献求助10
46秒前
小博carl应助LBJ23采纳,获得10
46秒前
缥缈冰珍完成签到 ,获得积分10
47秒前
迷路冰安完成签到 ,获得积分10
47秒前
王水苗完成签到,获得积分10
49秒前
爆米花应助璇77采纳,获得10
49秒前
SciGPT应助小曹采纳,获得10
51秒前
52秒前
高分求助中
Earth System Geophysics 1000
Semiconductor Process Reliability in Practice 800
Co-opetition under Endogenous Bargaining Power 666
Studies on the inheritance of some characters in rice Oryza sativa L 600
Medicina di laboratorio. Logica e patologia clinica 600
《关于整治突出dupin问题的实施意见》(厅字〔2019〕52号) 500
Language injustice and social equity in EMI policies in China 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3210755
求助须知:如何正确求助?哪些是违规求助? 2859947
关于积分的说明 8121707
捐赠科研通 2525516
什么是DOI,文献DOI怎么找? 1359388
科研通“疑难数据库(出版商)”最低求助积分说明 642979
邀请新用户注册赠送积分活动 614856