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Functional Implications of Cytoglobin, a Novel Protein, in Liver Fibrosis

Functional Implications of Cytoglobin, a Novel Protein, in Liver Fibrosis


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About the Book

This dissertation, "Functional Implications of Cytoglobin, a Novel Protein, in Liver Fibrosis" by Kwun-nok, Mimi, Man, 文冠諾, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled FUNCTIONAL IMPLICATIONS OF CYTOGLOBIN, A NOVEL PROTEIN, IN LIVER FIBROSIS Submitted by MAN Kwun Nok Mimi for the degree of Master of Philosophy at the University of Hong Kong in December 2006 Cytoglobin is a recently discovered hexacoordinate globin protein with a yet undefined function. It was found to be up-regulated in toxin-induced liver fibrosis and during hypoxic conditions in models. Though it has been documented to be mainly localized in fibroblasts in connective tissues in various organs and in hepatic stellate cells, there are controversies regarding its subcellular localization and its localization in certain cell types, e.g. hepatocytes. Cytoglobin has been hypothesized to function as a scavenger of reactive oxygen species, as a reservoir for the supply of oxygen during stress conditions, and in the metabolism of the extracellular matrix. The objective of this project is to delineate the functional property of cytoglobin by exploring its localization and its expression pattern in acute toxicological response towards the hepatotoxin carbon tetrachloride and during development of carbon tetrachloride-induced liver fibrosis in mouse. The localization of cytoglobin in normal mouse tissues was studied using immunohistochemistry. Cytoglobin was found to be expressed in fibroblasts in connective tissues around blood vessels in liver and other organs, as well as in the hepatic stellate cells. In the brain, cytoglobin was expressed in both the nuclei and cytoplasmic processes of certain neurons. The localization of cytoglobin in fibroblasts and hepatic stellate cells, which are the producers of extracellular matrix (ECM) in normal and disease states respectively, may imply a role in extracellular matrix metabolism. The expression pattern of cytoglobin and procollagen I alpha 1 chain (Col1a1), a molecule in the ECM, during acute liver injury caused by carbon tetrachloride was studied using immunohistochemistry and real-time polymerase chain analysis. Up-regulation of cytoglobin mRNA began at 12h and peaked at 24h post-administration with expression level over 3.5-fold higher than normal. The expression level of Col1a1 increased at 48h post-administration with over 7.5-fold up-regulation. The increase in expression of Col1a1 mRNA 24h following that of cytoglobin mRNA may imply a role for cytoglobin in metabolism of Col1a1. Alternatively, cytoglobin may be up-regulated for scavenging reactive species generated during acute liver injury, or act as an oxygen supplier to regions under histotoxic hypoxia during liver injury. To determine whether the expression of cytoglobin is correlated to the progression of liver fibrosis, the number of cytoglobin-expressing cells during the development of liver fibrosis was quantified and the expression level of cytoglobin mRNA in regions of fibrosis and in intact parenchyma was compared. The number of cytoglobin-expressing cells was found to increase with the severity of liver fibrosis until 6 weeks. Level of cytoglobin mRNA was higher in the parenchyma of mouse with 8 weeks' treatment as compared with that of normal. These results may represent a positive correlation of cytoglobin with liver fibrosis. DOI: 10.5353/th_b3882073 Subjects: Globin Globin genes - Expression Liver - Fibrosis


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Product Details
  • ISBN-13: 9781374676541
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 116
  • Weight: 286 gr
  • ISBN-10: 1374676543
  • Publisher Date: 27 Jan 2017
  • Binding: Paperback
  • Language: English
  • Spine Width: 6 mm
  • Width: 216 mm

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