TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions.

TGFbeta-induced protein (TGFBI) is an extracellular protein that mediates cell adhesion to collagen, laminin and fibronectin through its interaction with different beta integrins. We had previously reported that hypoxia-induced TGFBI mRNA expression in lymphatic endothelial cells (LEC). Here, we demonstrate that TGFBI can contribute to hypoxia-induced increases in LEC adhesion to the ECM. We show that while there are no changes in alpha1, alpha4, alphav, beta1, beta2, beta3, alpha5beta1, alphavbeta3, alphavbeta5 integrin expression on the LEC surface after hypoxia exposure, there exists an accumulation of TGFBI adaptor protein in LEC supernatants. We also demonstrate that hypoxia driven TGBFI expression is dependent on TGFbeta production by LEC. Furthermore, we show that TGFBI mediated LEC adhesion and migration through the ECM by its binding to the beta3 integrin. The identification of the specific mechanisms regulating LEC-ECM interactions may help us design new therapeutic applications for diseases in which lymphatic vessel function is compromised.

Use of the transforming growth factor-beta1 inhibitor peptide in periprosthetic capsular fibrosis: experimental model with tetraglycerol dipalmitate.

BACKGROUND: Capsular contracture is the most common specific complication associated with silicone prostheses. It is thought to be caused by the gradual retraction of the fibrous scar tissue that forms around the prosthesis. Molecular biology has made it possible to determine the role of transforming growth factor beta (TGF-beta) in the scar physiopathology of any fibrotic process, including periprosthetic capsular fibrosis. The effects on the inhibition of TGF-beta have also been demonstrated in experimental models of scar formation and fibrosis, which opens the way for new therapeutic alternatives in the treatment of capsular contracture. METHODS: Three experimental groups of 10 rats each were formed to evaluate periprosthetic fibrosis after its modulation with a newly synthesized TGF-beta1 peptide inhibitor in a tetraglycerol dipalmitate matrix. In the first group, subcutaneously and submuscularly placed, smooth, solid silicone prostheses were left untreated; in the second group, the prostheses were left after being immersed in a solution of tetraglycerol dipalmitate; and in the third group, following the same protocol as in the second group, the solution contained tetra-glycerol dipalmitate mixed with the inhibitor peptide of TGF-beta1. The animals were euthanized 8 weeks after implantation, and the capsules were assessed both macroscopically and histologically. RESULTS: Inhibition of capsular thickness and cellularity was significantly more effective in the group of animals treated with the inhibitor peptide of TGF-beta1. CONCLUSIONS: The TGF-beta1 inhibitor peptide applied in a matrix with tetraglycerol dipalmitate is significantly effective in achieving a reduction in periprosthetic fibrosis after placement of silicone implants, either subcutaneously or submuscularly. This result suggests new therapeutic approaches.

Utilización de Péptido Inhibidor de Transforming Growth Factor-b (TGF-b) en Fibrosis Capsular Periprotésica / Use of transforming growth factor-b inhibitor peptide in periprotheses capsular fibrosis

La contractura capsular es la complicación específica más frecuente relacionada con las prótesis de silicona, atribuida a una retracción lenta y progresiva del tejido fibroso cicatricial formado alrededor de las mismas, Su imprevisible aparición, variable en el tiempo, se manifiesta desde un ligero endurecimiento hasta una deformidad evidente provocando asimetrías, molestias, e incluso ruptura de la prótesis y dificultad en la expansión tisular. La biología molecular ha permitido determinar el papel del Transforming Growth Factor b (TGF-b) en la fisiopatología cicatricial de cualquier proceso fibrótico, incluida la fibrosis capsular periprotésica, y de la misma manera, ha demostrado los efectos de la inhibición del TGFb en modelos experimentales de cicatrización y fibrosis, sugiriendo nuevas alternativas terapéuticas en el tratamiento de esta complicación. El propósito de este estudio es valorar la fibrosis periprotésica de Silicona tras la modulación de la misma con un inhibidor peptídico de TGF-b de reciente síntesis. Se forman para ello tres grupos experimentales: en el primero, las prótesis tanto Subcutáneas (Sc) como submusculares (Sm), no sufrieron tratamiento alguno; en el Segundo, Se procedió a la inyección periprotésica de suero fisiológico (SF) con dimetil-sulfóxido (DMSO) durante 4 semanas a días alternos; en el tercer grupo, y siguiendo el mismo protocolo que en el grupo anterior, la inyección periprotésica Se realizó con el inhibidor de TGF-b. Los animales fueron sacrificados transcurridas ocho semanas de la implantación, valorándose las cápsulas formadas macroscópica e histológicamente. Tras el estudio Se comprobó que la inhibición es significativamente eficaz en las cápsulas de implantes de localización submuscular (AU)