Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10316/81285
Título: | A local uPAR-plasmin-TGFβ1 positive feedback loop in a qualitative computational model of angiogenic sprouting explains the in vitro effect of fibrinogen variants | Autor: | E. M. Boas, Sonja Carvalho, João van den Broek, Marloes M. Weijers, Ester Goumans, Marie-José Goumans, Marie-José Koolwijk, Pieter M. H. Merks, Roeland |
Data: | 6-Jul-2018 | Editora: | PLOS Computational Biology | Volume: | 14 | Número: | 7 | Resumo: | In experimental assays of angiogenesis in three-dimensional fibrin matrices, a temporary scaffold formed during wound healing, the type and composition of fibrin impacts the level of sprouting. More sprouts form on high molecular weight (HMW) than on low molecular weight (LMW) fibrin. It is unclear what mechanisms regulate the number and the positions of the vascular-like structures in cell cultures. To address this question, we propose a mechanistic simulation model of endothelial cell migration and fibrin proteolysis by the plasmin system. The model is a hybrid, cell-based and continuum, computational model based on the cellular Potts model and sets of partial-differential equations. Based on the model results, we propose that a positive feedback mechanism between uPAR, plasmin and transforming growth factor β1 (TGFβ1) selects cells in the monolayer for matrix invasion. Invading cells releases TGFβ1 from the extracellular matrix through plasmin-mediated fibrin degradation. The activated TGFβ1 further stimulates fibrin degradation and keeps proteolysis active as the sprout invades the fibrin matrix. The binding capacity for TGFβ1 of LMW is reduced relative to that of HMW. This leads to reduced activation of proteolysis and, consequently, reduced cell ingrowth in LMW fibrin compared to HMW fibrin. Thus our model predicts that endothelial cells in LMW fibrin matrices compared to HMW matrices show reduced sprouting due to a lower bio-availability of TGFβ1. | URI: | https://hdl.handle.net/10316/81285 | ISSN: | 1553-7358 | DOI: | 10.1371/journal.pcbi.1006239 | Direitos: | openAccess |
Aparece nas coleções: | I&D CFis - Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
journal.pcbi.1006239.pdf | 7.16 MB | Unknown | Ver/Abrir |
Citações SCOPUSTM
3
Visto em 15/abr/2024
Citações WEB OF SCIENCETM
20
2
Visto em 2/abr/2024
Visualizações de página
205
Visto em 23/abr/2024
Downloads
22
Visto em 23/abr/2024
Google ScholarTM
Verificar
Altmetric
Altmetric
Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.