Motonaga K, Itoh M, Hachiya Y, Endo A, Kato K, Ishikura H, Saito Y, Mori S, Takashima S, Goto Y
Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
J Clin Pathol. 2002 Mar;55(3):195-9. doi: 10.1136/jcp.55.3.195.
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.
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.
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.
These findings suggest that the age specific onset of WS may be related to age dependent expression of WRNp in specific organs.
沃纳综合征（WS）是一种罕见的常染色体隐性疾病，由人类WRN解旋酶（沃纳综合征蛋白，WRNp）的突变失活引起。WS患者在青春期后逐渐出现各种衰老特征。本研究的目的是确定WRNp的分布以及调节WRN基因表达的转录因子在多种人体器官中的表达，以试图了解WS的表型。
从16名年龄在27孕周至70岁的对照者以及一名56岁的WS女性患者获取组织标本。通过免疫组织化学和免疫印迹分析研究WRNp的分布以及调节WRN基因表达的转录因子——SP1、AP2和视网膜母细胞瘤蛋白（Rb）——在各种人体器官中的表达。
在青春期后的健康对照者中，在睾丸的生精上皮细胞和间质细胞、胰腺的腺泡、肾上腺皮质的束状带和网状带中检测到WRNp的高表达。此外，调节WRNp基因表达的SP1和AP2转录因子在WRNp表达的那些区域呈年龄依赖性出现。在青春期后的对照者中，SP1在睾丸和肾上腺中表达，而AP2在胰腺中表达。
这些发现表明，WS的年龄特异性发病可能与特定器官中WRNp的年龄依赖性表达有关。
