Publications (2)16.78 Total impact
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Article: Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice.
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ABSTRACT: Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42 in regulating liver regeneration. Using a mouse model with liver-specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy. Histological analysis, immunostaining, and western blot analysis were performed to characterize Cdc42LK livers and to explore the role of Cdc42 in liver regeneration. In control mouse livers, Cdc42 became activated between 3 and 24 hours after partial hepatectomy. Loss of Cdc42 led to a significant delay of liver recovery after partial hepatectomy, which was associated with reduced and delayed DNA synthesis indicated by 5-bromo-2'-deoxyuridine staining. Consistent with this, expression of cyclins D1, A, and E was markedly delayed or reduced in Cdc42LK livers during regeneration. As a potential effector of Cdc42, Rac1 activation was dramatically attenuated in Cdc42LK livers after partial hepatectomy, suggesting it is regulated in a Cdc42-dependent manner. Activation of certain proliferative signaling pathways, such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p70S6 kinase pathways, was delayed in Cdc42LK livers. In addition, dilated bile canaliculi and excessive lipid accumulation were observed in mutant livers during liver regeneration, which may result from impaired cytoskeletal organization and intracellular trafficking in hepatocytes. Conclusion: Our results revealed important roles of Cdc42 in the regulation of proliferative signaling during liver regeneration.Hepatology 01/2009; 49(1):240-9. · 11.66 Impact Factor -
Article: Proteomic profiling of regionalized proteins in rat epididymis indicates consistency between specialized distribution and protein functions.
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ABSTRACT: The epididymis is a key structure of the male reproductive system; its function is to mature, transport, and store sperm. Most of the research examining the epididymis to date has been limited to the study of the secreted proteins involved in the maturation of spermatozoa. However, it is also very important to understand the protein components, regulation and function of the tissue itself since these are the basis for all of its physiological processes. We investigated the differential expression of proteins among the caput, corpus, and cauda regions of rat epididymis and considered the possible links between the localization of these proteins and the different functions of these epididymal regions. High-resolution 2-D gel electrophoresis followed by mass spectrometry (MS) revealed 28 distinct proteins whose expression levels varied from the caput to the cauda epididymis. Sixteen of them were reported for first time to be expressed in the epididymis. Expression patterns of some proteins were validated by Northern blot or Western blot. Immunohistochemistry revealed that inducible carbonyl reductase (iCR), an important enzyme in the anti-oxidative system, exhibits primary and cell-type specific distribution in the distal cauda region. Moreover, analysis of iCR transcription in castrated animals showed that its expression is androgen-dependent. Together with its known functions, iCR may also be involved in androgen metabolism and maintaining a steady microenvironment in the duct of epididymis.Journal of Proteome Research 03/2006; 5(2):299-307. · 5.11 Impact Factor
