Differentielle Expression von Claudinen entlang des menschlichen Nephrons und in epithelialen Nierenzelltumoren
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Philipps-Universität Marburg
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Abstract
In multicellular organisms TJ are an essential part of cellular sheets in polar epithelia and in endothelial cells. They seal the intercellular space. Thereby they establish different compartments and maintain the polarized character of cells.
Recently the claudin family has been detected as an important player in the formation of TJ. Together with occludin they belong to the transmembrane proteins in TJ. It became clear that claudins show a tissue-specific expression pattern. Claudins can be expressed in different combinations and these combinations can be correlated with different values of transepithelial resistance. Therefore, we describe in this publication the celltype-specific expression pattern of claudins along the human nephron.
In immunhistochemical stainings on paraffin sections with antibodies against claudin 1, claudin 2, claudin 3, claudin 4, claudin 8 , claudin 11, occludin and ZO-1 the different parts of the human tubular system - identified by specific marker proteins - are characterized. It can be shown that every part of the nephron from the glomerulum up to the collecting duct shows its typical claudin expression. This expression pattern in combination with the actual knowledge in cellphysiology can be correlated with the different functions in resorption and elimination of solutes in the different parts of the tubular system. For example, the proximal tubule is characterized by the expression of claudin 2 which is known to form leaky TJ. In contrast there is no staining for claudin 2 but for claudin 4 in the collecting duct. This special claudin is correlated to a high transepithelial resistance in this part of the nephron. Moreover, it can be shown that kidney tissue of mice (published data) and human (this publication) seem to correspond on the substantial aspects.
Up to now, there are only very rare ultrastructural analysis on TJ in renal cell carcinomas. Therefore, we checked the expression of claudins in the three most common types of carcinomas in kidney, which are clear cell (n=11), papillary (n=10) and chromophobe (n=7) carcinoma. In showing stainings for occludin and ZO-1 it seems to be probable that there are TJ or at least rudimentary junctional structures in these carcinomas. Moreover, the carcinomas can be devided in three subgroups analysing the distribution of the different claudins. These subgroups match the pathological classification described above wich is the actual classification scheme of renal cell carcinomas. The clear cell type shows expression of claudin 2, the papillary type expression of claudin 2, claudin 3 and claudin 4 and the chromophobe type only expresses claudin 3 and claudin 4-
According to this findings the actual classification of renal cell carcinomas is supported by the expression pattern of the different claudins. Moreover, claudin 2 and claudin 4 can be used in immunhistochemical diagnostics, especially as long as moleculargenetic analysis are too expensiv.
We compare the expression pattern along the nephron to the tumor-specific one. These studies show that the common but not undiscussed concept of histogenesis of renal cell carcinomas can be proofed. The clear cell carcinoma seems to originate from cells of the proximal tubule, the chromophobe carcinoma from cells of the collecting duct. Only for the papillary type it remains still unclear even regarding the expression of claudins. The papillary type has got in intermediate position showing marker proteins that characterise not only the proximal tubule but also the collecting duct.
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Created: 2005Issued: 2006-01-30Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
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DoctoralThesis
Keywords
Tight junctionsNiereClaudineNierenzellkarzinomRenal cell carcinomasKidneyClaudins
DFG-subjects
Tight junction
DDC-Numbers
610
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Kemmer, Inken: Differentielle Expression von Claudinen entlang des menschlichen Nephrons und in epithelialen Nierenzelltumoren. : Philipps-Universität Marburg 2006-01-30. DOI: https://doi.org/10.17192/z2006.0005.
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This item has been published with the following license: In Copyright