HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gupta, S. Articles by Gorla, G. R. Search for Related Content PubMed PubMed Citation Articles by Gupta, S. Articles by Gorla, G. R. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 4, 2157-2165, January 22, 1999

Position-specific Gene Expression in the Liver Lobule Is Directed by the Microenvironment and Not by the Previous Cell Differentiation State

Sanjeev Gupta^§¶, Pankaj Rajvanshi^¶, Rana P. Sokhi^¶, Shilpa Vaidya^¶, Adil N. Irani^¶, and Giridhar R. Gorla^**

From the  Marion Bessin Liver Research Center and ^§ Cancer Research Center, Departments of ^¶ Medicine and ^** Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York 10461

Mechanisms directing position-specific liver gene regulation are incompletely understood. To establish whether this aspect of hepatic gene expression is an inveterate phenomenon, we used transplanted hepatocytes as reporters in dipeptidyl peptidase IV-deficient F344 rats. After integration in liver parenchyma, the position of transplanted cells was shifted from periportal to perivenous areas by targeted hepatic ablations with carbon tetrachloride. In controls, transplanted cells showed greater glucose-6-phosphatase and lesser glycogen content in periportal areas. This pattern was reversed when transplanted cells shifted from periportal to perivenous areas. Transplanted hepatocytes in perivenous areas exhibited inducible cytochrome P450 activity, which was deficient in periportal hepatocytes. Moreover, cytochrome P450 activity was rapidly extinguished in activated hepatocytes when these cells were transplanted into the nonpermissive liver of suckling rat pups. In cells isolated from the normal F344 rat liver, cytochrome P450 inducibility was originally greater in perivenous hepatocytes; however, periportal cells rapidly acquired this facility in culture conditions. These findings indicate that the liver microenvironment exerts supremacy over prior differentiation state of cells in directing position-specific gene expression. Therefore, persistence of specialized hepatocellular function will require interactions with regulatory signals and substrate availability, which bears upon further analysis of liver gene regulation, including in progenitor and/or stem cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R. D. Irwin, G. A. Boorman, M. L. Cunningham, A. N. Heinloth, D. E. Malarkey, and R. S. Paules Application of Toxicogenomics to Toxicology: Basic Concepts in the Analysis of Microarray Data Toxicol Pathol, January 1, 2004; 32(1_suppl): 72 - 83. [Abstract] [PDF]

				BASL abstracts Gut, May 1, 2003; 52(5): e1 - 31. [Full Text] [PDF]

				H. Malhi, G. R. Gorla, A. N. Irani, P. Annamaneni, and S. Gupta Cell transplantation after oxidative hepatic preconditioning with radiation and ischemia-reperfusion leads to extensive liver repopulation PNAS, October 1, 2002; 99(20): 13114 - 13119. [Abstract] [Full Text] [PDF]

				H. Malhi, A. N. Irani, S. Gagandeep, and S. Gupta Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes J. Cell Sci., January 7, 2002; 115(13): 2679 - 2688. [Abstract] [Full Text] [PDF]

				R. P. Sokhi, P. Rajvanshi, and S. Gupta Transplanted reporter cells help in defining onset of hepatocyte proliferation during the life of F344 rats Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G631 - G640. [Abstract] [Full Text] [PDF]

				S. Gupta and C. E. Rogler Lessons From Genetically Engineered Animal Models. VI. Liver repopulation systems and study of pathophysiological mechanisms in animals Am J Physiol Gastrointest Liver Physiol, December 1, 1999; 277(6): G1097 - G1102. [Abstract] [Full Text] [PDF]

				S. H. Sigal, P. Rajvanshi, G. R. Gorla, R. P. Sokhi, R. Saxena, D. R. Gebhard Jr., L. M. Reid, and S. Gupta Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1260 - G1272. [Abstract] [Full Text] [PDF]