RELIATECH: Angiogenesi e Linfoangiogenesi

RELIATECH: Angiogenesi e Linfoangiogenesi

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Angiogenesi (lo sviluppo di nuovi vasi sanguigni da un letto vascolare esistente), non è solo essenziale per molti processi fisiologici, ad esempio ovulazione, placentazione ed embriogenesi, ma anche in situazioni fisiopatologiche quali l’angiogenesi tumorale, retinopatia diabetica, artrite reumatoide, o psoriasi.

Linfoangiogenesi è tradizionalmente messa in ombra dalla maggiore enfasi posta sull’angiogenesi. Ciò è dovuto in parte alla mancanza di identificazione di fattori linfoangiogenici, così come dalla disponibilità di marcatori che distinguono sangue da endotelio vascolare linfatico. Recentemente, nuovi fattori di crescita, recettori, proteine â€‹â€‹della superficie cellulare, e fattori di trascrizione sono stati trovati in grado di svolgere un ruolo nella endotelio linfatico. Si tratta di VEGF-C, VEGF-D, VEGFR-3, LYVE-1, Podoplanin e Prox-1. Specialmente il fattore di trascrizione Prox-1 e i due Podoplanin recettori transmembrana e LYVE-1 sono descritti come marcatori specifici per cellule endoteliali linfatiche.

Anticorpi per Angiogenesi

Podoplanin, LYVE-1, PROX-1 e CD31, etc…

The circulation system consists of blood vessels and lymphatic vessels.
The lymphatic system plays important roles in immune function, homeostasis and tumor metastasis. Clinical observations indicate thatwhile sarcomas spread mainly through the blood stream, most carcinomas spread primarily via the lymphatic vessels.

In animal models, overexpression of lymphangiogenic factors VEGF-C and VEGF-D in tumor cells enhances metastatic spread of tumors. In the past, there were no reliable markers to distinguish blood vessel endothelial cells and lymphatic endothelial cells. Only recently several specific lymphatic markers have been discovered and „lymphangiogenesis“ is now emerging as an exciting sector of angiogenesis research, largely due to potential clinical applications.

We support this research with a collection of well-validated antibodies against human and mouse lymphatic markers podoplanin, PROX-1 and LYVE-1.

Podoplanin is a well-recognized lymphatic endothelium marker, which can be used to reliably distinguish lymphatic vessels from blood vessels.
Podoplanin is a Mr 38000 membrane mucoprotein that was originally detected on the surface of rat glomerular epithelial cells (podocytes) and was found to be linked to fl attening of foot processes that occur in glomerular diseases. Podoplanin shows features of a membrane mucoprotein with several conserved O-glycosylation sites. Currently, it is of unknown biological function. Because heavily O-glycosylated mucoproteins were identified recently as counterreceptors for selectins that mediate adhesion of infl ammatory cells, it is possible that podoplanin plays a similar role in lymphatic endothelia.

The homeobox gene PROX-1 was originally cloned by homology to the Drosophila melanogaster gene prospero. PROX-1 is expressed in a subpopulation of endothelial cells which by budding and sprouting, give rise to the lymphatic system. PROX-1-defi cient homozygous mice have unaffected vasculogenesis and angiogenesis, but liver and lymphatics do not develop. Human PROX-1 gene has been mapped to chromosome 1q32.2 – q32.3, and its product shows 94% similarity to the chicken protein. The conserved structure and expression pattern of the Prox-1 gene imply that it may play the same roles in humans as in other vertebrates. The human PROX-1 gene is most actively expressed in the developing lens. Our anti-PROX-1 provide a highly specifi c marker of lymphatic endothelial cells.

Double Immunostaining of human lymphatic endothelial cells using antibodies to
Podoplanin (green) and PROX-1 (red)

Antibody tools for studying lymphatic vessels
The combination of anti podoplanin, anti-LYVE-1 and anti-CD31 /PECAM1 antibodies can be used to differentiate clearly between blood vessels, lymphatic vessels and bile ducts in paraffi n embedded or frozen sections (see schema below). Furthermore they are useful for immunoprecipitation experiments and western blotting.

                  Podoplanin CD31
Lymphatic vessel    +        +
Blood vessel           –        +
Bile duct                 +        –

Paraffin sections of mouse liver stained with (anti mouse Podoplanin, (first) and anti mouse CD31 (second)

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