Regulation of biliary proliferation by alpha-calcitonin gene-related peptide : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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College Station, Tex. :
Texas A&M University System Health Science Center,
2006.
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| Subjects: |
| Abstract: | ABSTRACT: Cholestatic liver diseases represent a major public health concern leading to liver transplantation or mortality. The role of sensory innervation and neuropeptides in the regulation of liver physiology and cholestatic liver disease pathogenesis has not been studied thoroughly. In our study, we demonstrated that α-CGRP-positive sensory innervation plays a key role in the regulation of cholangiocyte proliferation and biliary mass during cholestasis induced by extrahepatic bile duct obstruction (BDL). We have shown that cholestasis induces proliferation of cholangiocytes with a dramatic increase in biliary mass, which was associated with concomitant increases circulating levels of CGRP. In vitro, α- and β-CGRP stimulated increased intracellular cAMP levels, activation of PKA and phosphorylation of CREB (Ser-133). Finally, we demonstrated that cholangiocyte proliferation induced by cholestasis was partially ablated in a knockout mouse model lacking the sensory neuropeptide α-CGRP. These findings indicated that sensory innervation of the liver plays a predominant role in the regulation of cholangiocyte proliferation and the pathogenesis of cholestatic liver diseases. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy December 2006." Approved as to style and content by: Gianfranco Alpini, Cynthia Meininger, Scott Supowit, Donald DiPette, Harris Granger. |
| Physical Description: | xi, 99 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 70-98). |