Mechanotransduction in lymphatic endothelial cells.
Initial lymphatic vessel endothelial cells are connected to the surrounding elastic fibers by fibrillin anchoring filaments that have been hypothesized to favor interstitial fluid drainage in edema pulling apart interendothelial junctions. We hypothesized a biochemical mechanism involving mechanotransduction. This study was designed to verify whether a relation exists between focal adhesion molecules and anchoring filaments and whether they may transduce extracellular forces to the nucleus. We first performed an immunohistochemical study on human skin cryostat sections to evaluate whether fibrillin and alphav-beta3 integrins, FAK and fibrillin, or alphav-beta3 integrins and FAK co-localize in lymphatic endothelium. We observed that integrins and FAK co-localize and that fibrillin filament attachment sites to endothelial cells merge with these molecules. These data may suggest that fibrillin anchoring filaments are connected to endothelial cells through focal adhesions. Mechanotransduction was investigated applying static stretching to bovine thoracic duct segments and lymphatic endothelial cells cultured on elastic membranes and immunohistochemically evaluating the expression of ERK1/2. Under stretching conditions, ERK1/2 labels the nucleus. Western blotting on cultured cells confirmed the presence of ERK1/2 in stretched cells. Based on our data we speculate that anchoring filaments may trigger a focal adhesion-mediated cascade of mechanotransduction toward the nucleus for genetic modulation and thus contribute to endothelial adaptation to interstitial requirements.
Department of Neuroscience, Molecular Medicine Section, University of Siena, Italy.
A
A
Rossi
E
E
Weber
G
G
Sacchi
D
D
Maestrini
F
F
Di Cintio
R
R
Gerli
D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism*; D000071837:Fibrillins; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D013897:Thoracic Duct / Q000166:cytology
D000071837:Fibrillins; D039302:Integrin alphaVbeta3; D008840:Microfilament Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3