ABSTRACT
Las fisuras labio palatinas se generan por la falta de fusión de los tejidos del labio o del paladar durante las primeras etapas del desarrollo fetal, estas se encuentran entre los defectos congénitos más comunes causados por el desarrollo facial anormal durante la gestación; su etiología no se encuentra totalmente aclarada, sin embargo se intenta explicar por medio del modelo de umbral multifactorial, planteándose que es producto de la interacción de factores endógenos y exógenos, entre los endógenos se han reportado alteraciones en la señalización del TGF-ß, el cual está involucrado en el desarrollo embrionario, diferenciación celular y en la regulación del desarrollo del paladar. En esta revisión se muestran los recientes avances sobre las implicaciones moleculares de la vía de señalización TGF-ß en el desarrollo de las fisuras labio palatinas (AU)
Cleft lip and palate are generated by the lack of fusion of the tissues of the lip or palate during early fetal development, these are among the most common birth defects caused by abnormal facial development during gestation. The etiology of these cracks is not fully elucidated, however attempts to explain by means of multifactorial threshold model, considering that is the product of the interaction of endogenous and exogenous factors, endogenous alterations have been reported in TGF-ß signaling, which is involved in embryonic development, cell differentiation and in the regulation of development of the palate. In this review, the recent advances implications of the molecular signaling pathway TGF-ß in the development of cleft lip and palate shown (AU)
Subject(s)
Humans , Transforming Growth Factor beta/genetics , Cleft Palate/genetics , Cleft Lip/genetics , Palate, Soft/embryology , Cleft Palate/embryology , Signal Transduction/genetics , Smad2 Protein/genetics , Smad3 Protein/geneticsABSTRACT
Oval cells constitute an interesting hepatic cell population. They contribute to sustain liver regeneration during chronic liver damage, but in doing this they can be target of malignant conversion and become tumor-initiating cells and drive hepatocarcinogenesis. The molecular mechanisms beneath either their pro-regenerative or pro-tumorigenic potential are still poorly understood. In this study, we have investigated the role of the HGF/c-Met pathway in regulation of oval cell migratory and invasive properties. Our results show that HGF induces c-Met-dependent oval cell migration both in normal culture conditions and after in vitro wounding. HGF-triggered migration involves F-actin cytoskeleton reorganization, which is also evidenced by activation of Rac1. Furthermore, HGF causes ZO-1 translocation from cell-cell contact sites to cytoplasm and its concomitant activation by phosphorylation. However, no loss of expression of cell-cell adhesion proteins, including E-cadherin, ZO-1 and Occludin-1, is observed. Additionally, migration does not lead to cell dispersal but to a characteristic organized pattern in rows, in turn associated with Golgi compaction, providing strong evidence of a morphogenic collective migration. Besides migration, HGF increases oval cell invasion through extracellular matrix, a process that requires PI3K activation and is at least partly mediated by expression and activation of metalloproteases. Altogether, our findings provide novel insights into the cellular and molecular mechanisms mediating the essential role of HGF/c-Met signaling during oval cell-mediated mouse liver regeneration.
