The
            <i>C. elegans pvf‐1</i>
            gene encodes a PDGF/VEGF‐like factor able to bind mammalian VEGF receptors and to induce angiogenesis

Tarsitano, Marina; Falco, Sandro De; Colonna, Vincenza; McGhee, James D.; Persico, M. Graziella

doi:10.1096/fj.05-4147com

Cited by 48 publications

(49 citation statements)

References 30 publications

(55 reference statements)

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“…The fruit fly Drosophila melanogaster has three PVFs (PVF-1-3), and a single PDGF/VEGF receptor (PVR). The nematode Caenorhabditis elegans has four receptors (VER-1-4), and one putative ligand (PVF-1) (Hoch and Soriano 2003;Tarsitano et al 2006), whose direct interaction with the VERs remains to be established. Invertebrate PVR/VERs resemble the mammalian VEGF receptors in that they have seven (rather than five) extracellular Ig loops.…”

Section: Invertebrate Pdgf/vegfsmentioning

confidence: 99%

Role of platelet-derived growth factors in physiology and medicine

Andræ¹,

Gallini²,

Betsholtz³

2008

Genes Dev.

2,026

1,898

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Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-␣ signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-␤ signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial-mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.Platelet-derived growth factor (PDGF) was identified more than three decades ago as a serum growth factor for fibroblasts, smooth muscle cells (SMCs), and glia cells (Kohler and Lipton 1974;Ross et al. 1974;Westermark and Wasteson 1976). Human PDGF was originally identified as a disulfide-linked dimer of two different polypeptide chains, A and B, separable using reversed phase chromatography (Johnsson et al. 1982). The B-chain (PDGF-B) was characterized by amino acid sequencing, revealing a close homology between PDGF-B and the product of the retroviral oncogene v-sis of simian sarcoma virus (SSV) (Doolittle et al. 1983;Waterfield et al. 1983). Subsequent studies confirmed that the human cellular counterpart (c-sis) was identical to PDGF-B and that autocrine PDGF activity was sufficient for SSV transformation in vitro. This was a paradigm-shifting discovery about the relationship between neoplastic cell transformation and normal growth control. For the first time, the importance of autocrine growth stimulation in neoplastic transformation was demonstrated. As discussed below, it is now well established that autocrine PDGF stimulation plays a role also in some human cancers.PDGF-A was characterized by cDNA cloning ). This resolved a paradoxical lack of correlation between secretion of PDGF-like growth factors from tumor cell lines and their expression of c-sis; it turned out that most such cell lines express PDGF-A and secrete PDGF-AA homodimers ). Together with the demonstration that PDGF-BB homodimers are produced by SSV-transformed or PDGF-Bexpressing cells, these results showed that the PDGF...

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Section: Invertebrate Pdgf/vegfsmentioning

confidence: 99%

Role of platelet-derived growth factors in physiology and medicine

Andræ¹,

Gallini²,

Betsholtz³

2008

Genes Dev.

2,026

1,898

View full text Add to dashboard Cite

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“…The C. elegans pvf-1 gene encodes a small secreted protein (PVF-1) with a VEGF-related sequence that includes the highly conserved positioning of cysteines characteristic of the VEGF/PDGF growth factor family (Tarsitano et al, 2006). C. elegans PVF-1 has been found to bind human receptors VEGFR1 (FLT1) and VEGFR2 (KDR), and can induce angiogenesis in chick embryos and capillary tube formation in human umbilical vein endothelial cell (HUVEC) culture (Tarsitano et al, 2006).…”

Section: Pvf-1 Expression Pattern and Genetic Characterisationmentioning

confidence: 99%

“…C. elegans PVF-1 has been found to bind human receptors VEGFR1 (FLT1) and VEGFR2 (KDR), and can induce angiogenesis in chick embryos and capillary tube formation in human umbilical vein endothelial cell (HUVEC) culture (Tarsitano et al, 2006). To study the function of PVF-1 in C. elegans, we first examined its expression pattern.…”

Section: Pvf-1 Expression Pattern and Genetic Characterisationmentioning

confidence: 99%

“…It was established previously that PVF-1 can substitute for VEGF in vertebrate angiogenesis (Tarsitano et al, 2006). To determine whether the converse is true, we introduced into the pvf-1(ev763); plx-1(ev724) double mutant a transgene array in which the myo-3 promoter drives body wall muscle expression of mouse VEGF-164.…”

Section: Pvf-1 Expression Pattern and Genetic Characterisationmentioning

confidence: 99%

“…elegans VERs (VEGF-related receptors) and vertebrate FLT and KDR VEGF receptors function in the PVF-1 signalling pathway for ray 1 positioning Because the vertebrate VEGF receptors are able to mediate VEGFlike signalling by PVF-1 in vertebrates (Tarsitano et al, 2006), we wondered whether putative vascular endothelial growth factor receptors (VERs) of C. elegans could also mediate PVF-1 signalling to position ray 1 in C. elegans males. Four ver genes that encode a family of four RTKs structurally related to VEGF receptors (VEGFRs) were identified previously (Popovici et al, 2002) and reported to express in specialised cells of neural origin such as glial support cells of amphid and phasmid neurons (VER-1), in the chemosensory ADL neurons (VER-2), and in the ALA neurons (VER-3) of C. elegans (Popovici et al, 2002).…”

Section: Research Article Development 140 (19)mentioning

confidence: 99%

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C. elegansPVF-1 inhibits permissive UNC-40 signalling through CED-10 GTPase to position the male ray 1 sensillum

et al. 2013

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Graded distributions of netrin and semaphorin guidance cues convey instructive polarity information to migrating cells and growth cones, but also have permissive (i.e. non-polarity determining) functions in mammalian development and repair. The permissive functions of these cues are largely uncharacterised at a molecular level. We found previously that UNC-6 (netrin) signals permissively through UNC-40 (DCC) and UNC-5 receptors to prevent anterior displacement of the ray 1 sensillum in the C. elegans male tail. UNC-6/UNC-40 signalling functions in parallel with SMP-1 (semaporin 1)/PLX-1 (plexin) signalling to prevent this defect. Here, we report that a deletion allele of pvf-1, which encodes a VEGF-related protein, causes no ray 1 defects, but enhances ray 1 defects of a plx-1 mutant, and unexpectedly also suppresses unc-6(ev400)-null mutant ray 1 defects. These mutant ray 1 inductive and suppressive effects are mimicked by the ability of unc-40(+) and ced-10(gain-of-function) multi-copy transgene arrays to induce ray 1 defects or suppress unc-6 mutant ray 1 defects, depending on their dosage, suggesting the pvf-1 mutation causes UNC-40 overactivity that interferes with signalling but is partially sensitive to UNC-6. Additional data suggest PVF-1 functions through four VEGF receptor-related proteins and inhibits only CED-10 (a GTPase), but not MIG-2-dependent UNC-40 activity, even though UNC-40 functions through both GTPases to position ray 1. pvf-1 and receptor mutant ray 1 defects are rescued by transgenes expressing mouse VEGF164 and human VEGF receptors, respectively. These data report the first case of VEGF-induced inhibition of the netrin signalling and a molecular conservation of VEGF function from worms to humans.

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Persistent sensitization of depressive‐like behavior and thermogenic response during maternal separation in pre‐ and post‐weaning guinea pigs

Schneider

Schiml

Deak

et al. 2011

Developmental Psychobiology

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Early attachment disruption is thought to promote later onset of depressive illness through a process involving sensitization. Maternal separation in guinea pig pups produces depressive-like behavior and core body temperature fluctuations that appear to be mediated by proinflammatory activity. In pups near the age of weaning (~20 days of age), these responses are increased during repeated separations occurring over several days. Here, enhanced depressive-like behavior and core body temperature responses were observed during repeated separations in guinea pigs from ~10 to 30 days of age. The sensitization lasted for more than a week, with the greatest temperature response occurring during the final separation. These results demonstrate persisting sensitization of behavioral and thermogenic responses to maternal separation over the age range in which these responses are known to occur. The findings are consistent with the hypothesis that proinflammatory activity contributes to the sensitization response and provide further suggestion that the impact of early attachment disruption on susceptibility to depression may involve proinflammatory processes.

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The C. elegans pvf‐1 gene encodes a PDGF/VEGF‐like factor able to bind mammalian VEGF receptors and to induce angiogenesis

Cited by 48 publications

References 30 publications

Role of platelet-derived growth factors in physiology and medicine

Role of platelet-derived growth factors in physiology and medicine

C. elegansPVF-1 inhibits permissive UNC-40 signalling through CED-10 GTPase to position the male ray 1 sensillum

Persistent sensitization of depressive‐like behavior and thermogenic response during maternal separation in pre‐ and post‐weaning guinea pigs

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