ABSTRACT
The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, alpha-catenin, alpha-SMA, vimentin, S100A4, TGF-beta1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and alpha-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, alpha-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-beta1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-beta1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Bile Ducts/cytology , Biomarkers/metabolism , Cell Differentiation/physiology , Epithelial Cells/cytology , Epithelium/physiology , Gallstones/metabolism , Liver Diseases/metabolism , Mesoderm/cytologyABSTRACT
Cholangiocytes (epithelial cells lining the intra- and extrahepatic bile ducts) and hepatocytes are two major components of liver epithelia. Although cholangiocytes are less numerous than hepatocytes, they are involved in both bile secretion and diverse cellular processes such as cell-cycle phenomena, cell signaling, and interactions with other cells, matrix components, foreign organisms, and xenobiotics. Cholangiocytes are also targets in several human diseases including cholangiocarcinoma, primary sclerosing cholangitis, autoimmune cholangitis, and vanishing bile-duct syndrome. The rapid advances in experimental biology technologies are greatly expanding interest in and knowledge of the physiology and pathophysiology of cholangiocytes. This review focuses on the progress of in vivo and in vitro experimental models in elucidating the physiologic functions of cholangiocytes and the pathophysiology of various cholangiopathies. The following aspects are reviewed: isolation of cholangiocytes from the liver and their heterogeneity, various culture systems, establishment of cholangiocyte cell lines, isolation and usage of intrahepatic bile-duct units, three-dimensional modeling of the bile duct, experimental models for inducing cholangiocyte proliferation, and various cholangiopathies such as cholangiocarcinoma, primary sclerosing cholangitis, and autoimmune cholangitis.
Subject(s)
Animals , Humans , Mice , Bile Duct Diseases/etiology , Bile Ducts/cytology , Disease Models, Animal , Epithelial Cells/metabolism , Imaging, Three-Dimensional , Models, AnimalABSTRACT
This paper has the objective to analyze the cellular aspects of liver regeneration (LR). Upon damage in this organ, the regenerative capacity of hepatocyte is sufficiently able to reestablish the parenchyma as a whole. Taking into account the regenerative capacity of hepatocyte, the need of a progenitor or a liver trunk cell was not obvious. Nowadays it is well-established that precursor cells take part in the liver regenerative process. The liver trunk cell, oval cell, acts as a bypotential precursor, contributing for the liver restoration, mainly when the hepatocytes are unable to proliferate. Another precursor, trunk cell of hematopoetic origin (HSC), takes part in the regenerative process, originating cells of the hepatocitic lineage and colangiocytes, as well as the oval cell. The way the trans-differentiation takes place is not established yet. A number of studies must be undertaken in order to clarify questions, such as the possible occurrence of cellular fusion process between the HSC and the hepatic cells and the possibility of application as a new therapeutic procedure in the treatment of diseases associated with insufficiency of this noble organ.
Este artigo tem como objetivo analisar aspectos da regeneração hepática (RH) sob a óptica celular. Em vigência de uma lesão neste órgão a capacidade regenerativa do hepatócito é suficientemente capaz de restabelecer o parênquima como um todo. Levando em conta a elevada capacidade regenerativa do hepatócito, a necessidade de um progenitor ou uma célula tronco hepática não era óbvia. Hoje esta bem estabelecido que células precursoras participam do processo regenerativo hepático. A célula tronco hepática, célula oval, atua como um precursor bipotencial, contribuindo para o restauro do fígado principalmente quando os hepatócitos se encontram impossibilitados de proliferar. Um outro precursor, a célula tronco de origem hematopoética (HSC), participa do processo regenerativo, originando células da linhagem hepatocítica e colangiócitos, assim como a células oval. Ainda não está estabelecido o meio como ocorre o fenômeno de transdiferenciação.Muitos estudos devem ser realizados no intuito de esclarecer questões, tais como a possível ocorrência de processo de fusão celular entre a HSC e as células hepáticas e a possibilidade de ser aplicado como uma nova terapêutica no tratamento de doenças associadas à insuficiência deste nobre órgão.