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Venugopal Gunda, Raj K. Verma, Chandra S. Boosani, Sudhakar A. Yakkanti; Alpha 6 Type IV Collagen Non-Collagenous Domain Regulates Elastin and VGVAPG Activated Choroidal Endothelial Cell Migration and Tube Formation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2958.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization evident in age related macular degeneration involves the migration and tube formation by choroidal endothelial cells, which are regulated through the extracellular matrix components. Elastins and their derivative bioactive peptide, VGVAPG play pathological roles by promoting endothelial cell (EC) migration and tube formation in choroidal neovascularization. The type IV collagen derived non-collagenous domains (NC1) are known to exhibit anti-angiogenic properties and inhibit neovascularization. However, the effect of any of the type IV collagen NC1 domain on elastin mediated angiogenesis was not studied. We have evaluated the effect of type IV collagen alpha 6 chain derived non-collagenous domain [α6(IV)NC1] on elastin and VGVAPG mediated angiogenic effects in-vitro.
Recombinant human α6(IV)NC1 was cloned and purified from transformed E.coli for in vitro evaluations. Effect of purified α6(IV)NC1 on kappa elastin, mouse elastin and VGVAPG mediated mouse choroidal endothelial cell (MCEC) migration and tube formation were studied using Boyden chamber and Matrigel methods respectively. MMP-14 levels from cell culture supernatants and cell lysates of elastin-, VGVAPG- and α6(IV)NC1- treated MCEC cultures were also evaluated using western blot analyses.
Recombianat α6(IV)NC1 inhibited mouse choroidal endothelial cell migration and tube formation activated by kappa elastin, mouse elastin and the bioactive peptide VGVAPG. α6(IV)NC1 also showed effect on elastin and VGVAPG mediated MMP-14 secretion by MCECs.
Recombinant α6(IV)NC1 inhibits elastin and VGVAPG stimulated angiogenesis in vitro. Elastin and VGVAPG mediated MCEC migration and tube formation are inhibited by α6(IV)NC1. Elastin and VGVAPG mediated MMP-14 secretion by MCEC are inhibited by α6(IV)NC1. The mechanism of action of α6(IV)NC1 and its in-vivo potential are yet to be deciphered.
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