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|Title: ||The Role of Adiponectin and T-cadherin Interactions in Liver Fibrosis|
|Authors: ||Alzahrani, Badr Ali B.|
|Issue Date: ||12-Oct-2015|
|Publisher: ||University of Sydney|
Sydney Medical School
|Abstract: ||Liver fibrosis results in a loss of liver function, and contributes to over 1.4 million deaths every year worldwide. Adiponectin, an adipocytokine, has been shown to have an important role in the suppression of fibrosis. Adiponectin binds to three receptors—AdipoR1, AdipoR2 and T-cadherin. The overarching aim of this thesis was to examine the role of adiponectin and T-cadherin interactions in liver fibrosis, using mouse and cellular models. Liver fibrosis was induced in wild-type (WT), adiponectin (APN) knockout (KO), T-cadherin (Tcad) KO, and APN-Tcad double KO mice using intraperitoneal injections of CCl4. Isolated primary rat HSCs were treated with APN receptor specific small interfering ribonucleic acid (siRNA), followed by subsequent treatment with recombinant APN. The results demonstrated that liver fibrosis was significantly increased in the APN KO mice, reduced in the Tcad KO mice, and unchanged in the DKO mice compared to the WT control mice. Tcad was responsible for sequestering APN to the liver. In response to APN, HSCs activity, migration, and proliferation were reduced. In addition, the knockdown of Tcad reduced HSC proliferation and the fibrotic response, independent of APN. Thus, it is possible that Tcad is a worthy therapeutic target for treating liver fibrosis in humans.|
|Access Level: ||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions: ||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
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|ALZAHRANI Badr - Final Thesis.pdf||Thesis||36.99 MB||Adobe PDF|
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