TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish

Abstract

Key Words: TRPC1 Ⅲ VEGF Ⅲ ISV Ⅲ angiogenesis Ⅲ zebrafish T he vascular system of vertebrates consists of a stereotyped and highly branched network of arteries, veins, and capillaries. This network extends into every tissue of the body and is tailored to its local physiological function. [1][2][3] The development of vascular networks requires 2 successive processes, vasculogenesis and angiogenesis. 1,2 During vasculogenesis, mesoderm-derived hemangioblasts differentiate in situ into endothelial cells (ECs), which coalesce at the midline to form a lumenized vascular plexus. 1,2 This primary network subsequently expands through angiogenesis, which is characterized by the growth of new blood vessels from preexisting ones. 1,2 Numerous ligands and their receptors have been identified to exert positive or negative regulation on angiogenesis, including vascular endothelial growth factor (VEGF)/ VEGF receptors, angiopoietin/Tie and notch/␦-like 4, [3][4][5][6][7][8] and their downstream signaling pathways have also been partially elucidated. [3][4][5][6][7] For example, VEGF-induced angiogenesis is mainly attributable to the activation of both Mitogen-activated protein kinase/extracellular signalregulated kinase (ERK)1/2 cascade and AKT/protein kinase B pathway. 9 Angiopoietin1/Tie2-induced EC migration during angiogenesis is largely mediated by the activation of phosphoinositide 3-kinase signaling pathway. 8 There is increasing evidence that guidance of vessels and nerves during development share common underlying mechanisms. [2][3][4][5][6]10,11 Some axon guidance molecules, such as ephrins, netrins, and slits, also influence angiogenic sprouting. 3,6,7,10,11 Recent studies have shown that Ca 2ϩ -permeable transient receptor potential type C channels (TRPCs) 12 are downstream effectors of the axon guidance molecules netrin-1, brain-derived neurotrophic factor and myelinassociated glycoprotein, and are required for axon guidance triggered by these cues. [13][14][15] The TRPC family is composed of 7 members in mammals (TRPC1 to -7). 12 In the vascular Original received March 19, 2009; resubmission received August 19, 2009; revised resubmission received February 10, 2010; accepted February 11, 2010. From [17][18][19] However, the role of TRPCs in vascular development remains largely unknown. The goal of this study is to investigate whether TRPCs are important for angiogenesis in vivo.The zebrafish has emerged as a powerful vertebrate model system for in vivo study of vascular development. 20 Transgenic lines with vascular ECs expressing fluorescent proteins allow imaging of blood vessel growth in live embryos. 21,22 Moreover, a range of reverse genetic methods, including the antisense morpholino oligonucleotide (MO)-based knockdown approach, 23,24 have been developed for manipulating gene expression and function in zebrafish. 25 Recently, zebrafish trpc1 was identified. It is highly homologous to mammalian trpc1 and ubiquitously expressed postfertilization until 24 hours. 26 In the present study, we examined the...

Transient Receptor Potential Canonical Channels Are Required for in Vitro Endothelial Tube Formation

“…On EA.hy926 cells, TRPC6 knockdown slightly reduced tube formation, a marginal effect compared with the important effect of TRPC3, TRPC4, and TRPC5 knockdown. TRPC1 was shown to have a prominent role in angiogenesis in zebrafish (33), but in mammals, no further data reported a role of TRPC channels in tube formation (14).…”

New Insight on the Role of Transient Receptor Potential (TRP) Channels in Driven Gliomagenesis Pathways

“…In vivo time-lapse imaging revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. TRPC1 acts synergistically with VEGFA in controlling ISV growth, and appeared to be downstream to VEGFA in controlling angiogenesis (Yu et al, 2010). Recently a role for TRPC1 in hypoxia-induced VEGF expression in U87 glioma cells has been reported.…”

“…Studies in zebrafish, have demonstrated that the involvement of TRPCs channels in angiogenesis represents a reminiscent of the role of TRPC channels in axon guidance (Yu et al, 2010). Activation of TRPC1 seems to be essential for the angiogenesis in vivo.…”

Functional properties of ion channels and transporters in tumour vascularization

“…Remarkably, TRPC1 is proangiogenic in vivo: knockdown of zebrafish TRPC1 by morpholinos caused severe angiogenic defects in intersegmental vessel sprouting, presumably owing to impaired filopodia extension during EC migration [62] (table 1 and figure 2). …”

“…HMEC, human microvascular EC; HPAEC, human pulmonary artery EC; HUVEC, human umbilical vein EC; EA.hy926, EC line derived from HUVEC fused with human lung adenocarcinoma cell line A549; PAEC, porcine aortic endothelial cells; BTEC, tumour-derived EC from breast carcinoma; H5VEC, heart endothelioma (H5V) EC; MAEC, mouse aortic EC; EPC, endothelial progenitor cells; RCC-EPC, EPC isolated from renal carcinoma patients; Numbers in parenthesis indicate the respective reference number. EPC [30] HMEC [31] BTEC [32] RCC-EPC [29] HUVEC [33 -35] HUVEC [36] HUVEC [37] HUVEC [38] HUVEC [36,39] MAEC from KO mice [40] HMEC [41,42] EPC [43] survival and proliferation RCC-EPC [29] EPC [30] HMEC [31] HUVEC [44] PAEC [45] H5V EC [46] HUVEC [40] HUVEC, HMEC [41,55] EPC [43] permeability HMEC,HUVEC [56 -58] HPAEC [59] Frog mesenteric microvessels [60] H5V EC [46] HUVEC [61] in vivo angiogenesis zebrafish [62] CAM [44] collateral growth [45] HERG-1-Retinoblastoma [63] EAG1-Xenograft in SCID mice and human osteosarcoma [27,28] CAM [54] xenograft in nude mice [38] Rabbit cornea [64] human mammary carcinoma, glioblastoma [65,66] AQP1 KO mice and C57BL/ 6 mice …”