Mechanotransduction in lymphatic endothelial cells

Initial lymphatic vessel endothelial cellsare connected to the surrounding elastic fibersby fibrillin anchoring filaments that havebeen hypothesized to favor interstitial fluiddrainage in edema pulling apart interendothelialjunctions. We hypothesized abiochemical mechanism involving mechanotransduction.This study was designed to verifywhether a relation exists between focaladhesion molecules and anchoring filamentsand whether they may transduce extracellularforces to the nucleus. We first performed animmunohistochemical study on human skincryostat sections to evaluate whether fibrillinand αv-β3 integrins, FAK and fibrillin, orαv-β3 integrins and FAK co-localize inlymphatic endothelium. We observed thatintegrins and FAK co-localize and thatfibrillin filament attachment sites toendothelial cells merge with these molecules.These data may suggest that fibrillinanchoring filaments are connected toendothelial cells through focal adhesions.Mechanotransduction was investigatedapplying static stretching to bovine thoracicduct segments and lymphatic endothelial cellscultured on elastic membranes andimmunohistochemically evaluating theexpression of ERK1/2. Under stretchingconditions, ERK1/2 labels the nucleus.Western blotting on cultured cells confirmedthe presence of ERK1/2 in stretched cells.Based on our data we speculate thatanchoring filaments may trigger a focaladhesion-mediated cascade of mechanotransductiontoward the nucleus for geneticmodulation and thus contribute to endothelialadaptation to interstitial requirements.