Differentiation Of Sinusoidal Endothelial Cells Research Articles

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells.

We examined the gene expression profiles of the 5-hydroxytryptamine signaling pathway in the regenerating liver and 8 types of liver cells during rat liver regeneration, and explored expression differences in 5-hydroxytryptamine signaling pathway genes at the level of tissues and cells, as well as the role of the pathway on liver regeneration. Eight types of rat regenerating liver cells were isolated using Percoll density-gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5-hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21, 16, 19, 22, 27, and 20 genes changed significantly in hepatocytes, biliary epithelial cells, hepatic stellate cells, oval cells, sinusoidal endothelial cells, Kupffer cells, pit cells, dendritic cells, and the regenerating liver, respectively. Synthetic effects of 5-hydroxytryptamine signaling pathway genes in 8 types of liver cells showed that 26 genes were expressed significantly; the expression trends of 10 genes were the same in the regenerating liver, while others were different. Based on the gene expression profiles of the 8 types of liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway. There were large differences in genes involved in 5-hydroxytryptamine signaling at the tissue and cellular levels; thus, liver regeneration should be studied in-depth at the cellular level to reveal the molecular mechanism of liver regeneration.

Involvement of signaling of VEGF and TGF-β in differentiation of sinusoidal endothelial cells during culture of fetal rat liver cells

Embryonic development of the liver is closely associated with vascular organization. However, little is known about the mechanisms of vascular differentiation during liver development. Our previous study showed that the maturation of sinusoidal endothelial cells (SECs) occurred during embryonic day 13.0 (E13.0) to E15.0. To improve our understanding of SEC differentiation, we examined here the expression of maturation markers, SE-1 and stabilin-2, in fetal livers and also attempted to establish an in vitro SEC differentiation system by culturing E13.5 fetal liver cells. Immunohistochemical examination of SE-1 and stabilin-2 expression during fetal rat liver development revealed that these differentiation markers were co-expressed in SECs in the late stage of liver development, although stabilin-2 was expressed in almost all vascular endothelial cells in the early stage. Liver cells from the E13.5 rat fetus were cultured in EBM-2 medium containing vascular endothelial growth factor (VEGF), transforming growth factor beta1 (TGF-beta1) and VEGF plus SB-431542 (an inhibitor of the TGF-beta1 receptor, activin receptor-like kinase 5 [ALK-5]). In vitro SEC differentiation, as indicated by the appearance of cells co-expressing SE-1 and stabilin-2 and of cells with cytoplasmic fenestrae in endothelial sheets, was induced by the addition of both VEGF and SB-431542, an inhibitor of the phosphorylation of Smad2/3 but not that of Smad1/5/8 in the cultured cells. These results indicate for the first time that both VEGF signaling and the blocking of the ALK-5-Smad2/3 signal pathway are important for the fetal differentiation of SECs.

Origin of endothelial cells from mesothelial-derived mesenchymal cells in the liver of avian embryos

We have tested the hypothesis of an origin of mesenchyme from the coelomic mesothelium of the developing avian liver and the differentiation of sinusoidal endothelial cells from mesothelial-derived mesenchymal cells. Our results have shown that 1) Mesothelial cells of the developing liver and the submesothelial mesenchymal cells are simultaneously cytokeratin (CK) and vimentin (VIM) immunoreactive between HH18 and HH28.2) A number of early sinusoidal cells are also CK immunoreactive. In the quail, CK colocalizes with the vascular marker QH1 in these cells. 3) In late embryos (>HH30), only the mesothelium remains CK+. 4) Mesothelial and submesothelial mesenchymal cells express the transcription factors Slug and WT1, both related to the epithelial-mesenchymal transition. 5) When the surface mesothelium was stained in vivo with CCFSE, a carboxyfluorescein derivative, isolated sinusoidal cells were labelled after 24-48 h, These observations suggest that mesenchymal cells originate from the coelomic mesothelium of the developing liver and differentate into endothelial cells of the hepatic sinusoids.

Angiogenesis of liver metastases: role of sinusoidal endothelial cells.

Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from pre-existing blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells are involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in BD IX rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal antibody. In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histological differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 microm, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.

Structural and Functional Differentiation of Sinusoidal Endothelial Cells During Liver Organogenesis in Humans

During fetal life, human liver sinusoids, which differentiate between 4 and 12 weeks of gestation from capillaries of the septum transversum, must support an important hematopoietic function and acquire the structural and functional characteristics of adult sinusoids. To gain insight into their differentiation process, we studied the expression of (1) markers of continuous endothelia, absent from adult sinusoidal endothelial cells (PECAM-1, CD34, and 1F10); (2) functional markers of adult sinusoidal endothelial calls (CD4, 1CAM-1, CD32, and CD14); and (3) extracellular matrix components (laminin, tenascin, fibronectin, and thrombospondin) in 37 fetuses of different gestational ages. We identified two successive differentiation events. (1) An early structural differentiation, occurring from 5 to 12 weeks of gestation, was characterized by the loss of continuous endothelial cell markers and a reduction in the perisinusoidal amount of laminin and in the deposition of tenascin, fibronectin, and thrombospondin; at the end of this process, fetal liver sinusoids present structural characteristics comparable to those of the sinuses in adult hematopoietic bone marrow. (2) A later functional differentiation was characterized by the acquisition of the markers of adult sinusoidal endothelial cells, initiating at 10 weeks of gestation and completed by 20 weeks of gestation; this process likely contributes to adapt liver sinusoids to the specific functions of the adult hepatic tissue.

The differentiation of sinusoidal endothelial cells (SEC) during liver organogenesis in humans

The differentiation of sinusoidal endothelial cells (SEC) during liver organogenesis in humans