CELSR1 Is a Positive Regulator of Endothelial Cell Migration and Angiogenesis.
Cadherin is an epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a key component of the noncanonical Wnt/planar cell polarity (PCP) pathway that critically regulates endothelial cell proliferation and angiogenesis. In this study, we examined the biological significance of CELSR1 in endothelial cell migration and angiogenesis. For this, we applied both gain-of-function and loss-of-function approaches. To increase the endogenous expression of CELSR1, we used the transcription activator-like effector (TALE) technology and constructed an artificial TALE-VP64 activator. To knock down the expression of CELSR1, we generated lentivirus containing short hairpin RNA sequences targeting different regions of CELSR1 mRNA. Following up- or down-regulation of CELSR1 in human aortic endothelial cells (HAEC), we assessed in vitro cell proliferation by MTT assay, migration by scratch and transwell migration assays, and angiogenesis by tube formation analysis. We found that CELSR1 was endogenously expressed in human umbilical vein endothelial cells (HUVEC) and HAEC. When focusing on HAEC, we found that upregulating CELSR1 expression significantly promoted cell growth, while knocking down CELSR1 inhibited the growth (p < 0.05). Using both scratch and transwell migration assays, we observed a positive correlation between CELSR1 expression and cell migratory capability. In addition, CELSR1 upregulation led to higher levels of tube formation in HAEC, while downregulating CELSR1 expression decreased tube formation (p < 0.05). Mechanistically, CELSR1-regulated migration and tube formation was mediated through disheveled segment polarity protein 3 (Dvl3). In conclusion, CELSR1 plays an important role in regulating multiple phenotypes of endothelial cells, including proliferation, migration, and formation of capillary-like structures.
The First Affiliated Hospital of Xiamen University, Department of Neurology, Xiamen, 361003, China. qilinma@yeah.net.
Yi-Hong
YH
Zhan
Qi-Cong
QC
Luo
Xiao-Rong
XR
Zhang
Nai-An
NA
Xiao
Cong-Xia
CX
Lu
Cen
C
Yue
Ning
N
Wang
Qi-Lin
QL
Ma
D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
C454220:CELSR1 cadherin, human; D015820:Cadherins; D034741:RNA, Small Interfering