Peng-chun Yu1, Shan-ye Gu, Ji-wen Bu, Jiu-lin Du. 1. Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Abstract
RATIONALE: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development. OBJECTIVE: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development. METHODS AND RESULTS: Knockdown of zebrafish trpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide-resistant form of zebrafish trpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell-autonomous. In vivo time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a-induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase. CONCLUSIONS: These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.
RATIONALE: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development. OBJECTIVE: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development. METHODS AND RESULTS: Knockdown of zebrafishtrpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide-resistant form of zebrafishtrpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell-autonomous. In vivo time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a-induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase. CONCLUSIONS: These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.
Authors: Weijun Pan; Van N Pham; Amber N Stratman; Daniel Castranova; Makoto Kamei; Kameha R Kidd; Brigid D Lo; Kenna M Shaw; Jesus Torres-Vazquez; Constantinos M Mikelis; J Silvio Gutkind; George E Davis; Brant M Weinstein Journal: Blood Date: 2012-05-30 Impact factor: 22.113
Authors: A Fiorio Pla; H L Ong; K T Cheng; A Brossa; B Bussolati; T Lockwich; B Paria; L Munaron; I S Ambudkar Journal: Oncogene Date: 2011-06-20 Impact factor: 9.867