Identification of an angiogenic mitogen selective for endocrine gland endothelium

Abstract

The known endothelial mitogens stimulate growth of vascular endothelial cells without regard to their tissue of origin. Here we report a growth factor that is expressed largely in one type of tissue and acts selectively on one type of endothelium. This molecule, called endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), induced proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. However, EG-VEGF had little or no effect on a variety of other endothelial and non-endothelial cell types tested. Similar to VEGF, EG-VEGF possesses a HIF-1 binding site, and its expression is induced by hypoxia. Both EG-VEGF and VEGF resulted in extensive angiogenesis and cyst formation when delivered in the ovary. However, unlike VEGF, EG-VEGF failed to promote angiogenesis in the cornea or skeletal muscle. Expression of human EG-VEGF messenger RNA is restricted to the steroidogenic glands, ovary, testis, adrenal and placenta and is often complementary to the expression of VEGF, suggesting that these molecules function in a coordinated manner. EG-VEGF is an example of a class of highly specific mitogens that act to regulate proliferation and differentiation of the vascular endothelium in a tissue-specific manner.

Bv8, the amphibian homologue of the mammalian prokineticins, modulates ingestive behaviour in rats

“…In preliminary experiments, recombinant human PK-2, the mammalian orthologue of Bv8, also displayed potent dipsogenic and anorexigenic activity. These results overall confirm that Bv8 reproduces the effects of mammalian prokineticins not only on angiogenesis (LeCouter et al, 2001), intestinal motility (Li et al, 2001) and nociception (Negri et al, 2002) but also on drinking and feeding.…”

“…The small protein Bv8, isolated from amphibian skin (Mollay et al, 1999), belongs to a novel family of secreted proteins whose homologues have been found in snakes (Dendroaspis polylepsis: VPRA or MIT-1, Joubert & Strydom, 1980;Schweitz et al, 1999), rodents (mouse: mBv8 or prokineticin 2 (mPK-2), Wechselberger et al, 1999; rat: prokineticin 1 and 2 (rPK-1, rPK-2), Masuda et al, 2002) and humans (prokineticin 1 (PK-1) or EG-VEGF and prokineticin 2 (PK-2), Li et al, 2001;LeCouter et al, 2001). Common structural motives in this peptide family are the amino-terminal sequence of 20 amino-acid residues and the five disulphide bonds that link the 10 cysteine residues and fold the molecules into a globular form.…”

“…Common structural motives in this peptide family are the amino-terminal sequence of 20 amino-acid residues and the five disulphide bonds that link the 10 cysteine residues and fold the molecules into a globular form. The distribution of mRNAs of murine Bv8-like proteins has been reported in the brain, spinal cord, gastrointestinal tract, endocrine glands and other peripheral organs of mice and rats LeCouter et al, 2001;Li et al, 2001;Melchiorri et al, 2001;Cheng et al, 2002;Masuda et al, 2002). In the brain, the main localizations of mPK-2 include the olfactory bulb, cerebral cortex (in some neurones of layer II), dorsal and ventral hippocampus, medial preoptic area of the hypothalamus, suprachiasmatic nucleus (SCN), some thalamic nuclei, Purkinje cells of cerebellum, sensory and motor nuclei of the brain stem and spinal cord.…”

Prokineticins are neuroprotective in models of cerebral ischemia and ischemic tolerance in vitro

“…Hypoxic conditions in human adrenal carcinoma (LeCouter et al, 2001) or experimental stroke (Cheng et al, 2012) are known to induce the transcription of prokineticins. However, the results of experimental studies are conflicting on whether these chemokines may exert a protective or deleterious role in neurodegeneration.…”

VEGF Expression in Hypoxia and Hyperglycemia

“…Furthermore, VEGF is a vascular permeability factor, possibly acting by promoting endothelial fenestration (8). The role of VEGF in the maintenance of highly permeable and extensive vasculature in different tumors and in endocrine organs has been established (9).…”