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. 2002 Mar;55(3):195-9.
doi: 10.1136/jcp.55.3.195.

Age Related Expression of Werner's Syndrome Protein in Selected Tissues and Coexpression of Transcription Factors

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Free PMC article

Age Related Expression of Werner's Syndrome Protein in Selected Tissues and Coexpression of Transcription Factors

K Motonaga et al. J Clin Pathol. .
Free PMC article

Abstract

Aims: Werner's syndrome (WS) is an uncommon autosomal recessive disease resulting from mutational inactivation of human WRN helicase, Werner's syndrome protein (WRNp). Patients with WS progressively develop a variety of aging characteristics after puberty. The aim of this study was to determine the distribution of WRNp and the expression of the transcription factors regulating WRN gene expression in a variety of human organs in an attempt to understand the WS phenotype.

Methods: Tissue specimens were obtained from 16 controls aged from 27 gestational weeks to 70 years of age and a 56 year old female patient with WS. The distribution of WRNp and the expression of the transcription factors regulating WRN gene expression-SP1, AP2, and retinoblastoma protein (Rb)- were studied in the various human organs by immunohistochemical and immunoblot analyses.

Results: In the healthy controls after puberty, high expression of WRNp was detected in seminiferous epithelial cells and Leydig cells in the testis, glandular acini in the pancreas, and the zona fasciculata and zona reticularis in the adrenal cortex. In addition, the SP1 and AP2 transcription factors, which regulate WRNp gene expression, appeared in an age dependent manner in those regions where WRNp was expressed. In controls after puberty, SP1 was expressed in the testis and adrenal gland, whereas AP2 was expressed in the pancreas.

Conclusions: These findings suggest that the age specific onset of WS may be related to age dependent expression of WRNp in specific organs.

Figures

Figure 1
Figure 1
Immunoperoxidase staining of the organs, showing age dependent changes in Werner's protein (WRNp) immunoreactivity. Pancreas at (A) 11 years and (D) 32 years; seminiferous tubules in the testis at (B) 11 years and (E) 32 years; cortex of the adrenal gland at (C) 11 years and (F) 32 years. Arrows indicate the WRNp positive cells. F, zona fasciculata; R, zona reticularis. Scale bar, l μm.
Figure 2
Figure 2
Immunoperoxidase staining of the organs, showing age dependent changes in SP1 immunoreactivity. Pancreas at (A) 11 years and (D) 32 years; seminiferous tubules in the testis at (B) 11 years and (E) 32 years; cortex of the adrenal gland at (C) 11 years and (F) 32 years. Arrows indicate SP1 positive cells. F, zona fasciculata; R, zona reticularis. Scale bar, l μm.
Figure 3
Figure 3
Immunoperoxidase staining of the organs, showing age dependent changes in AP2 immunoreactivity. Pancreas at (A) 11 years and (D) 32 years; seminiferous tubules in the testis at (B) 11 years and (E) 32 years; cortex of the adrenal gland at (C) 11 years and (F) 32 years. Arrows indicate AP2 positive cells. F, zona fasciculata; R, zona reticularis. Scale bar, l μm.
Figure 4
Figure 4
Immunoblot of cytosol extracts probed with the anti-WRNp antibody, showing age dependent changes in Werner's protein (WRNp) immunoreactivity. Lanes 1–3, tissues from the control subject at 27 gestational weeks: frontal lobe (lane 1), pancreas (lane 2), kidney (lane 3); lanes 4–6, tissues from the 11 year old control subject: frontal lobe (lane 4), pancreas (lane 5), kidney (lane 6); lanes 7–9, tissues from the 64 year old control subject: frontal lobe (lane 7), pancreas (lane 8), kidney (lane 9). Antiserum demonstrated the presence of the 170 kDa WRNp in the pancreas from the 64 year old control subject. An aliquot of 50 μg of extracted protein was applied to each lane. The lower figure shows immunoblot analysis of actin as a control for loading.

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