2026-04-13T13:13:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1203242025-11-20T13:51:12Zcom_2072_1057col_2072_478798col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Del Valle-Pérez, Beatriz author Martinez, Vanesa Gabriela author Lacasa Salavert, Cristina author Figueras i Amat, Agnès author Shapiro, Sandor S. author Takafuta, Toshiro author Casanovas i Casanovas, Oriol author Capellá, G. (Gabriel) author Ventura Pujol, Francesc author Viñals Canals, Francesc author 2018-02-28T11:04:45Z 2018-02-28T11:04:45Z 2010-04-02 2018-02-28T11:04:45Z Actin-binding proteins filamin A (FLNA) and B (FLNB) are expressed in endothelial cells and play an essential role during vascular development. In order to investigate their role in adult endothelial cell function, we initially confirmed their expression pattern in different adult mouse tissues and cultured cell lines and found that FLNB expression is concentrated mainly in endothelial cells while FLNA is more ubiquitously expressed. Functionally, siRNA-knockdown of endogenous FLNB in HUVEC inhibited Vascular Endothelial Growth Factor (VEGF)-induced in vitro angiogenesis by decreasing endothelial cell migration capacity, whereas FLNA ablation did not alter these parameters. Moreover, FLNB-depleted cells increased their substrate adhesion with more focal adhesions. The molecular mechanism underlying this effect implicates modulation of small GTP binding protein Rac-1 localization and activity, with altered activation of its downstream effectors p21 protein Cdc42/Rac-activated kinase (PAK)-4/5/6 and its activating guanine nucleotide exchange factor Vav-2. Moreover, our results suggest the existence of a signaling complex including FLNB, Rac-1 and Vav-2 under basal conditions that would further interact with VEGFR2 and integrin αVβ5 after VEGF stimulation. In conclusion, our results reveal a crucial role for FLNB in endothelial cell migration and in the angiogenic process in adult endothelial cells. Proteïnes citosquelètiques Endoteli Migració cel·lular Angiogènesi Cytoskeletal proteins Endothelium Cell migration Neovascularization Filamin B plays a key role in VEGF-induced endothelial cell motility through its interaction with Rac-1 and Vav-2