Disease relevance of VTN

• TCC deposits were always observed with concomitant deposits of vitronectin (S-protein) in membranoproliferative glomerulonephritis, in contrast to a piglet with mesangial glomerulopathy where TCC was present without vitronectin co-deposition [1].
• These experimental aneurysms were embolized with standard GDCs (n = 23), collagen GDC-Is (n = 11), vitronectin GDC-Is (n = 6), laminin GDC-Is (n = 4), fibrinogen GDC-Is (n = 6), and fibronectin GDC-Is (n = 6) [2].
• The alphavbeta3 integrin, also known as vitronectin receptor, is an adhesive glycoprotein that promotes angiogenesis in the embryo and tumors such as melanoma [3].

High impact information on VTN

• SMCs exposed to EDHB or DHP attached normally to collagen- and vitronectin-coated substrates; however, spreading on collagen but not vitronectin was inhibited [4].
• In contrast, exposure of SMCs to vitronectin (1.0 micrograms/cm2) or thrombospondin (0.25 micrograms/cm2), two known ligands for alphaVbeta3, resulted in enhancement of the IGF-I-stimulated IRS-1 response [5].
• The mechanism of action of HRGP involves rearrangement of focal adhesions and decreased attachment of endothelial cells to vitronectin and, as a consequence, reduced endothelial cell migration [6].
• Blockade of alpha(V)beta(3) engagement or phospholipase C activity resulted in a strong inhibition of smooth muscle cell spreading on vitronectin [7].
• We demonstrate that alpha(V)beta(3) and alpha(V)beta(5) integrins synergistically regulate smooth muscle cell migration onto vitronectin [7].

Biological context of VTN

• Vitronectin is a multifunctional glycoprotein regulating the fibrinolysis, complement, and coagulation systems in plasma, besides exhibiting cell-spreading activity [8].
• Porcine vitronectin, the most compact form of single-chain vitronectin: the smallest molecular mass among vitronectins was ascribed to deletion and substitution of base pairs, and proteolytic trimming of the peptide [8].
• One amino acid substitution resulted in the loss of a potential glycosylation site in accordance with the finding on glycopeptide analyses that porcine vitronectin contained two kinds of glycosylated sequences, while human vitronectin contained three [8].
• Many of the functions of VN are mediated by a glycosaminoglycan binding site, near its carboxyl-terminal end [9].
• The role of YadA, UspA1, and UspA2H as eukaryotic cell adhesins and the function of UspA2 as a vitronectin binder led to our investigation of the cell adhesion and vitronectin binding properties of DsrA [10].

Anatomical context of VTN

• A third group interfered with the ability of vitronectin to inhibit complement-mediated guinea pig erythrocyte reactive lysis [11].
• Vitronectin (VN) is an adhesive glycoprotein with roles in the complement, coagulation, and immune systems [9].
• During early granulation tissue formation of wound repair, new capillaries invade the fibrin clot, a process that undoubtedly requires an interaction of vascular cells with the wound provisional matrix composed mainly of fibrin, fibronectin, and vitronectin [12].
• Extracellular matrix stimulation of guinea pig megakaryocyte proplatelet formation in vitro is mediated through the vitronectin receptor [13].
• The alpha 4, alpha 5, alpha v, beta 1, and beta 3 integrin subunits, vitronectin, and fibronectin were detected at sites of attachment between uterine epithelial cells and trophectoderm on Days 12-15 of pregnancy [14].

Associations of VTN with chemical compounds

• In this study, the complete primary structure of porcine vitronectin was elucidated by cloned cDNA and glycoprotein analyses [8].
• Reactivity of the antibody which inhibited heparin binding greatly increased upon denaturation of vitronectin, implying that this region is normally inaccessible in the native form of the molecule [11].
• Linear epitopes for the antibodies were identified using cyanogen bromide and plasmin-derived peptides from vitronectin [11].
• Dextran sulfate of average molecular mass 500 kDa was more effective than dextran sulfate of average molecular mass 5 kDa, supporting a template mechanism of action of the GAGs, in which VN molecules align on the GAG in a conformation suitable for cross-linking [9].
• We then theorized that DsrA might use vitronectin as a bridge to bind to human cells, but this hypothesis proved to be untrue as eliminating HaCaT cell binding of vitronectin with a monoclonal antibody specific to integrin alpha(v)beta(5) did not affect the attachment of H. ducreyi to HaCaT cells [10].

Other interactions of VTN

• Bone sialoprotein (BSP) and osteopontin (OPN) are two major non-collagenous proteins in bone that have similar biochemical properties and can mediate cell attachment through an RGD (Arg-Gly-Asp) motif that recognizes the vitronectin receptor [15].

Analytical, diagnostic and therapeutic context of VTN

• Oligosaccharides were released from the vitronectin by N-glycosidase F digestion and tagged with 2-aminopyridine, and the pyridylamino-oligosaccharides were fractionated by anion-exchange and reverse-phase HPLC [16].

References