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Objective To establish Cdh5-Cre ERT /Acta2-tdTomato-STOP floxed -eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre ERT /Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl 4 -induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre ERT /Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre ERT /Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.
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Nonalcoholic fatty liver disease (NAFLD) is a clinical metabolic syndrome characterized by hepatic steatosis, inflammation, and fibrosis and has become a common chronic liver disease with great impact on public health. Liver sinusoidal endothelial cells (LSECs) are specialized vascular endothelium of liver tissue, and as an important vascular barrier, LSECs play an important role in regulating the absorption and metabolism of nutrients and substances from the blood of the intestines in hepatocytes. This article reviews the research advances in LSEC capillarization, vascular dysfunction, and its involvement in the regulation of liver inflammation, angiogenesis, and liver fibrosis during the development and progression of NAFLD.
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With the continuous development of the cancer stem cell theory,biomarkers for CSCs (Cancer stem cells) have gradually become the hot issues in tumor research.As the most commonly used CSCs biomarker,CD44 gains lots of attentions.This paper will review recent research about CD44 molecule and its powerful role in regulating tumor progenesis and progression.
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Compelling evidences have shown that various types of cancer,including hepatocellular carcinoma,are originated from stem cells.The occurrenee,chemoresistance,metastasis and recurrence of hepatocellular carcinoma are associated with a small population of cells called cancer ster cells.Although the origin of hepatocellular carcinoma and hepatic cancer stem cells remain controversial after a decade of intensive investigation,increasing scholars tend to believe that hepatocellular carcinoma and hepatic cancer stem cells can derive from malignant transformation of hepatic stem cells being exposed to various kinds of carcinogens.In this review,we mainly focus on the recent progress on malignant transformation of hepatic stem cells.
RESUMO
Nonalcoholic fatty liver disease (NAFLD) is a clinical metabolic syndrome characterized by hepatic steatosis, inflammation, and fibrosis and has become a common chronic liver disease with great impact on public health. Liver sinusoidal endothelial cells (LSECs) are specialized vascular endothelium of liver tissue, and as an important vascular barrier, LSECs play an important role in regulating the absorption and metabolism of nutrients and substances from the blood of the intestines in hepatocytes. This article reviews the research advances in LSEC capillarization, vascular dysfunction, and its involvement in the regulation of liver inflammation, angiogenesis, and liver fibrosis during the development and progression of NAFLD.