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Protein expression of nuclear receptors in human and murine tissues

So Takegoshi1, Shuying Jiang, Riuko Ohashi

  • 1Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Pathology International
|January 22, 2009
PubMed

Insights

New monoclonal antibodies reveal tissue-specific expression of nuclear receptors (NR) in human and mouse tissues. This research highlights potential roles for NR in pancreatic alpha-cells, offering insights into diabetes mellitus.

Area of Science:

  • Molecular Biology
  • Immunology
  • Endocrinology

Background:

  • Nuclear receptors (NR) are crucial transcriptional regulators involved in development and metabolic homeostasis.
  • Understanding the tissue-specific expression of NR is vital for elucidating their diverse physiological roles.
  • Existing tools for NR detection may lack the specificity or applicability for detailed tissue analysis.

Purpose of the Study:

  • To generate and validate novel mouse anti-human monoclonal antibodies against various nuclear receptors.
  • To investigate the tissue-specific expression patterns of nuclear receptors in human and murine liver and pancreas.
  • To explore potential novel roles of specific nuclear receptors in pancreatic cell function and their implications for diabetes mellitus.

Main Methods:

  • Generation of mouse anti-human monoclonal antibodies against various nuclear receptors.
  • Specificity confirmation using immunoblotting with overexpressed proteins and intrinsic tissue proteins.
  • Application of validated antibodies for immunohistochemistry on human and murine liver and pancreas tissues.

Main Results:

  • Successfully generated 60 monoclonal antibodies, with 32 proving effective for immunohistochemistry.
  • Confirmed tissue-specific expression patterns of nuclear receptors in human and murine liver and pancreas.
  • Identified expression of hepatocyte nuclear factor 4alpha (HNF4alpha) and progesterone receptor in pancreatic alpha-cells, but not beta-cells.

Conclusions:

  • The newly developed monoclonal antibodies are powerful tools for detecting tissue-specific NR localization.
  • The findings suggest previously unrecognized roles for HNF4alpha and progesterone receptor in pancreatic alpha-cells.
  • This research provides a foundation for future studies on nuclear receptors in human and murine tissues, particularly concerning diabetes mellitus.

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