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Title: | 探討Ankyrin Repeat-rich Membrane Spanning(ARMS)蛋白在多囊性腎病與肝內膽道疾病之生物功能 The Role of Ankyrin Repeat-rich Membrane Spanning (ARMS) in Polycystic Kidney Disease and Intrahepatic Biliary Tree Disease |
Authors: | Mu-Shiun Tsai 蔡牧勳 |
Advisor: | 黃佩欣 |
Keyword: | 多囊性腎病,肝內膽道囊狀疾病,組織微陣列,組織免疫染色, ARMS,polycystic kidney,intrahepatic biliary cystic lesion,tissue array,immunohistochemistry, |
Publication Year : | 2008 |
Degree: | 碩士 |
Abstract: | Ankyrin repeat-rich membrane spanning (簡稱ARMS)為一神經細胞表現之膜蛋白,其功能為調控神經纖維的生長與維持神經肌肉接點。然而對於ARMS在其他正常的、病態的組織或細胞的表現,卻尚未曾被探討過。利用在組織微陣列上進行的ARMS免疫組織染色,我們發現ARMS特別表現在唾液管腺、皮膚汗腺與腎小管。同時,我們發現ARMS和KIF3A在腎小管的表皮細胞上有部分表現在同一位置,其位置是在細胞質與管腔面的細胞膜。由於過去的研究顯示KIF3A基因剔除小鼠會產生多囊性腎病,促使我們進一步探究是否ARMS的表現在人類的多囊性腎病上也有所變化。在二十個多囊性腎病的台大醫院病理部確診之案例中(民國89年至97年),ARMS免疫組織染色發現到ARMS在囊泡的表面細胞出現異常表現並且有在細胞核內表現 (廿個案例中的廿個均有此現象)。相比較之下,單純性腎囊腫只在細胞質有微弱至中等強度的ARMS表現,而表現在細胞核內的情形極為罕見(廿個案例中的五個有此現象)。此等觀察到的現象,使吾等推測ARMS在細胞核的異常性表現在人類的多囊性腎病具有特異性。同時,在另一與多囊性腎病高度相關的疾病:多囊性肝病中,其囊泡表面細胞中,則有新生的ARMS表現,並且也有在細胞核的表現。在其他肝內膽道囊狀腫瘤,其囊泡表面細胞則同樣有ARMS的新生表現情況。因此我們假設,在腎臟或是肝臟囊泡性疾病中,ARMS對於形成泡囊的過程中可能扮演著重要角色。 Ankyrin repeat-rich membrane spanning (ARMS) is a tetra-membranous protein enriched in neurons, and it regulates neurite growth and maintenance of neuromuscular junction. Whether ARMS is expressed in other tissue or cell type, diseased or not, is not investigated. By ARMS immunohistochemistry on tissue arrays composed of normal human tissues, we reported that ARMS is specifically expressed in ductal epithelia of salivary gland ducts, of skin eccrine ducts and of renal tubules. We further demonstrated that in renal tubules, ARMS was partially colocalized with KIF3A in the cytoplasm and apical membrane of renal tubular epithelium. Based on the fact that KIF3A-null results in polycystic kidney in mutant mice, we explored whether ARMS was aberrantly expressed in human renal polycystic disease. Immunohistochemistry in 20 cases of human polycystic kidney disease enrolled in Department of Pathology, National Taiwan University (2000-2008) revealed that ARMS was aberrantly and strongly expressed in the nucleus of the epithelium lining the cysts (20/20 cases). Whereas in contrast, almost all cases diagnosed as simple renal cysts showed weak to moderate ARMS-immunoreativity in the cytoplasm, but rarely in the nucleus (5/20). This observation suggests that ectopic nuclear localization of ARMS is specifically correlated with human polycystic kidney disease. Adding into complexity, ARMS could be neo-expressed and localized in the nucleus of those cystic epithelia lining hepatic polycystic liver, which is often associated with polycystic kidney disease. Examination of other intrahepatic biliary cystic neoplasms revealed neo-expression of ARMS in the cells lining these cysts. We hypothesize that ARMS might play an important role in mediating cyst formation originating specifically from renal or biliary tubular epithelium. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40370 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 病理學科所 |
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