Dicer is required for proper liver zonation

Shigeki Sekine, Reiko Ogawa, Michael T. Mcmanus, Yae Kanai, Matthias Hebrok

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

A number of genes and their protein products are expressed within the liver lobules in a region-specific manner and confer heterogeneous metabolic properties to hepatocytes; this phenomenon is known as 'metabolic zonation'. To elucidate the roles of Dicer, an endoribonuclease III type enzyme required for microRNA biogenesis, in the establishment of liver zonation, we examined the distribution of proteins exhibiting pericentral or periportal localization in hepatocyte-specific Dicer1 knockout mouse livers. Immunohistochemistry showed that the localization of pericentral proteins was mostly preserved in Dicer1-deficient livers. However, glutamine synthetase, whose expression is normally confined to a few layers of hepatocytes surrounding the central veins, was expressed in broader pericentral areas. Even more striking was the observation that all the periportal proteins that were examined, including phosphoenolpyruvate carboxykinase, E-cadherin, arginase 1, and carbamoyl phosphate synthetase-I, lost their localized expression patterns and were diffusely expressed throughout the entire lobule. Thus, with regard to periportal protein expression, the consequences of Dicer loss were similar to those caused by the disruption of β-catenin. An analysis of livers deficient in β-catenin did not identify the down-regulation of Dicer1 or any microRNAs, indicating that they are not directly activated by β-catenin. Thus, the present study illustrates that Dicer plays a pivotal role in the establishment of liver zonation. Dicer is essential for the suppression of periportal proteins by Wnt/β-catenin/TCF signalling, albeit it likely acts in an indirect manner.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalJournal of Pathology
Volume219
Issue number3
DOIs
Publication statusPublished - 2009 Nov
Externally publishedYes

Fingerprint

Catenins
Liver
Hepatocytes
Cadherins
Proteins
MicroRNAs
Carbamoyl-Phosphate Synthase (Ammonia)
Endoribonucleases
Wnt Proteins
Arginase
Glutamate-Ammonia Ligase
Phosphoenolpyruvate
Knockout Mice
Veins
Down-Regulation
Immunohistochemistry
Enzymes

Keywords

  • β-catenin
  • Dicer
  • Liver
  • Zonation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sekine, S., Ogawa, R., Mcmanus, M. T., Kanai, Y., & Hebrok, M. (2009). Dicer is required for proper liver zonation. Journal of Pathology, 219(3), 365-372. https://doi.org/10.1002/path.2606

Dicer is required for proper liver zonation. / Sekine, Shigeki; Ogawa, Reiko; Mcmanus, Michael T.; Kanai, Yae; Hebrok, Matthias.

In: Journal of Pathology, Vol. 219, No. 3, 11.2009, p. 365-372.

Research output: Contribution to journalArticle

Sekine, S, Ogawa, R, Mcmanus, MT, Kanai, Y & Hebrok, M 2009, 'Dicer is required for proper liver zonation', Journal of Pathology, vol. 219, no. 3, pp. 365-372. https://doi.org/10.1002/path.2606
Sekine S, Ogawa R, Mcmanus MT, Kanai Y, Hebrok M. Dicer is required for proper liver zonation. Journal of Pathology. 2009 Nov;219(3):365-372. https://doi.org/10.1002/path.2606
Sekine, Shigeki ; Ogawa, Reiko ; Mcmanus, Michael T. ; Kanai, Yae ; Hebrok, Matthias. / Dicer is required for proper liver zonation. In: Journal of Pathology. 2009 ; Vol. 219, No. 3. pp. 365-372.
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