Ekspresi reseptor retinoid X (α dan β) dalam diabetes autoimun
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Date
2005
Authors
Zulkarnain, Mustapha
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Abstract
The non-obese diabetic (NOD) mouse is an animal model of autoimmune diabetes, type 1
diabetes mellitus (T1DM) that spontaneously develops autoimmune diabetes between the
the ages of 9 to 30 weeks of life. The major pathological event in these mice is
mononuclear cell infiltration into the islets of Langerhans, known as insulitis, mainly by
macrophages, T lymphocytes and B lymphocytes. Retinoid X receptor (RXR) plays an
important role in regulating the morphogenesis, development, growth and differentiation of
cell and may be involved in the regulation of immune response. It also acts as a major
heterodimer partner with other nuclear receptors such as PPARs, RAR and VDR. The aim
of this study was to analyze the mRNA expression of two RXR isoforms in splenic T
lymphocyte CD4+ and CD8+ of NOD mice using quantitative real time polymerase chain
reaction. Splenic CD4+ and CD8+ T cells were isolated from three groups of NOD mice,
specifically five week old (NOD5), nine week old (NOD9) and diabetic group (dNOD).
Total RNA was isolated and cDNA was synthesized from each cell subset. The same
procedures were also carried out on groups of the non-obese resistance (NOR) mice,
namely NOR5, NOR9 and dcNOR (diabetic-control NOR) which served as age-matched
controls to the NOD mice. The expression levels of the RXR isoforms in each subset of T
lymphocytes were quantified by real time PCR using specifically developed homologous
internal standards for each RXR isoform. In addition, the levels of RXR proteins in the pancreas of both NOD and NOR mice were also studied using immunohistochemistry.
This research demonstrated that RXRα and RXRβ were differentially expressed in the
splenic CD4+ and CD8+ T cells. RXRα mRNA expression was found to be significantly
decreased in both CD4+ and CD8+ T cells of NOD mice compared to NOR mice in all age
groups. In contrast, RXRβ mRNA expression was significantly higher in both CD4+ and
CD8+ T cells of NOD mice compared to NOR mice at pre diabetic stage but decreased at
diabetic stage. These findings suggest that alterations of mRNA expression of both RXR
subtypes may be important in the development and progression of T1DM. Meanwhile,
only RXRα protein was observed in both NOD and NOR mice at pre diabetic and diabetic
stages, whereas RXRβ was not detected. The expression of RXRα protein was observed
only in the islets of Langerhan and not in the acinus cells in the pancreas, suggesting that
only this type of RXR receptor isoform plays a significant role in the physiology of the
pancreas.
Description
Master
Keywords
Medical science , Diabetes