Uroplakine

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Uroplakine ( ancient Greek : οὖρον ouron 'urine', 'urine'; ἡ πλαξ e plax 'the plate', 'the sheet', 'the board') are a group of proteins in the cell membrane of epithelial cells of the urothelium in the urinary bladder , ureter and Renal pelvis . The different uroplakines are partly responsible for the mechanical and chemical resistance of the lower urinary tract . Thus uroplania ("the leakage and diffusion of urine to other parts" of the body) is prevented.

Occurrence

There are four different Uroplakine. One is encoded by the Uroplakin Ib gene ( abbreviated : UP-Ib gene; English UPK1B gene). This gene is located on chromosome 19 , is 31 kDa in size and consists of eight exons . Exon 1 does not code (i.e. it is not translated into RNA ). Uroplakins occur mainly in the outer membrane of the umbrella cells of the urothelium. This is where they are most strongly expressed . In addition, uroplakins were also found in the stomach , kidneys , prostate , epididymis , testes ( sperm ) and ovaries ( oocytes ). The UP-Ib gene is overexpressed in 50% of the malignant tumors of the transitional epithelium (= urothelial carcinoma , English transitional cell carcinoma, TCC ) . H. more active than in non-malignant cells.

Barrier function

The human organs that permanently carry urine, the renal pelvis , ureters and bladder , are lined with a robust urothelium . This layer of cells forms a barrier and prevents toxic substances in the urine from damaging the tissue below. To achieve this barrier, the urothelium has tight junctions between the cover cells and glycans , special lipids and uroplakins on the surface . The uroplakins I, II and III together form the AUM ( asymmetrical unit membrane ), a highly specialized biomembrane that is characteristic of the surface of the epithelium of the bladder . This biomembrane contains semi-crystalline, hexagonal protein particles with a size of 12 nm .

Uroplakin species

In 1990, the research group of Sun and co-workers reported that the outer membrane of the cover cells in the urothelium of the bovine contains four different proteins: uroplakin-1a (UP-Ia), uroplakin-1b (UP-Ib), uroplakin-2 (UP- II) and Uroplakin-3 (UP-III). All of these proteins could later be cloned and sequenced . Analogous proteins have also been found in humans. Uroplakin-1a and Uroplakin-1b belong to the transmembrane 4 superfamily ( tetraspanins ). Uroplakin III is a glycoprotein , so it also contains carbohydrates in addition to protein . Wu and Sun have further elucidated the structure of Uroplakin III. The glycoprotein has a size of 47 kDa . After the carbohydrate component has been separated off by glycosidases , a protein of size 28.9 kDa remains. The extracellular component of Uroplakin III, i.e. the part that lies outside the actual cell membrane, has a size of 40 kDa, of which the protein accounts for 20 kDa and the carbohydrate part 20 kDa. The intracellular domain is only 5 kDa.

In 2002, Sun's working group published the discovery of another urothelial-specific protein. This was initially called p40. Because of its structure, it was then called Uroplakin IIIb. Uroplakin-III has been called Uroplakin-IIIa since then. So there are five different great posters.

Immunohistochemistry of urothelial carcinomas

Antibodies against Uroplakin II in combination with GATA-3 and p40 have proven themselves in immunohistochemical diagnostics. In 71 out of 90 cases (about 80%) of muscle-invasive urothelial carcinomas, the immune reaction to Uroplakin II was positive. There was also a significant positive correlation with GATA-3. A primary tumor as well as lymph node metastases could be examined histologically in 35 patients. In 90% of the tumors that were primarily Uroplakin positive, the lymph node metastases also reacted positively. Uroplakin is therefore important for determining the primary tumor in the case of metastases from an unknown primary tumor ( CUP ).

Lobban and co-workers examined tissues from nine non-invasive and eight invasive human urothelial carcinomas. Uroplakin-Ia and Uroplakin-II were found by in situ hybridization in the well- differentiated transitional cells of papillary carcinomas. Uroplakin-IB was positive in 7 of 9 non-invasive and 4 of 8 invasive tumors. Uroplakin-IB was expressed in the same way in lymph node metastases as in the primary tumor.

Wang et al. Performed immunohistochemical studies on small cell carcinoma (SmCC) of the bladder. The reaction to Uroplakin-II was positive in only one of 22 determinations.

Several companies supply antibodies against uroplakins for various purposes, including against UPK1A, UPK1B, UPK2, UPK3A and UPK3B in rabbits .

Individual evidence

  1. ^ Ludwig August Kraus: Kritisch-Etymologisches medicinisches Lexikon , 3rd edition, Verlag der Deuerlich- und Dieterichschen Buchhandlung, Göttingen 1844, p. 1078.
  2. ↑ J. Olsburgh, R. Weeks, P. Selby, J. Southgate: Human uroplakin lb gene structure and promoter analysis. In: Biochimica et Biophysica Acta . Volume 1576, Number 1-2, June 2002, pp. 163-170, PMID 12031497 .
  3. ↑ Y. Liao, HC Chang, FX Liang, PJ Chung, Y. Wei, TP Nguyen, G. Zhou, S. Talebian, LC Krey, FM Deng, TW Wong, JU Chicote, JA Grifo, DL Keefe, E. Shapiro , H. Lepor, XR Wu, R. DeSalle, A. Garcia-España, SY Kim, TT Sun: Uroplakins play conserved roles in egg fertilization and acquired additional urothelial functions during mammalian divergence. In: Molecular Biology of the Cell . [Electronic publication before going to press] October 2018, doi : 10.1091 / mbc.E18-08-0496 , PMID 30303751 .
  4. Jump up ↑ Q. Wan, G. Xiong, G. Liu, TD Shupe, G. Wei, D. Zhang, D. Liang, X. Lu, A. Atala, Y. Zhang: Urothelium with barrier function differentiated from human urine-derived stem cells for potential use in urinary tract reconstruction. In: Stem Cell Research & Therapy . Volume 9, number 1, November 2018, p. 304, doi : 10.1186 / s13287-018-1035-6 , PMID 30409188 , PMC 6225683 (free full text).
  5. ↑ XR Wu, T.-T. Sun: Molecular cloning of a 47 kDa tissue-specific and differentiation-dependent urothelial cell surface glycoprotein. In: Journal of Cell Science , 1993; Volume 106 (Part 1): pp. 31-43.
  6. ↑ a b c J. Yu, M. Manabe, XR Wu, C. Xu, B. Surya, TT Sun: Uroplakin I: a 27-kD protein associated with the asymmetric unit membrane of mammalian urothelium. In: The Journal of Cell Biology . Volume 111, Number 3, September 1990, pp. 1207-1216, PMID 1697295 , PMC 2116275 (free full text).
  7. ↑ XR Wu, T.-T. Sun: Molecular cloning of a 47 kDa tissue-specific and differentiation-dependent urothelial cell surface glycoprotein. In: Journal of Cell Science 1993; Volume 106 (Part 1): pp. 31-43.
  8. ↑ F.-M. Deng, F.-X. Liang, L. Tu, KA Resing, P. Hu, M. Supino, C.-CA Hu, G. Zhou, M. Ding, G. Kreibich, T.-T. Sun: Uroplakin IIIb, a urothelial differentiation marker, dimerizes with uroplakin Ib as an early step of urothelial plaque assembly. In: The Journal of Cell Biology 2002; Volume 159, Issue 4: pp. 685-694. doi: 10.1083 / jcb.200204102
  9. ↑ MZ Leivo, PJ Elson, DE Tacha, B. Delahunt, DE Hansel: A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma. In: Pathology . Volume 48, number 6, October 2016, pp. 543-549, doi : 10.1016 / j.pathol.2016.05.008 , PMID 27594510 .
  10. ↑ ED Lobban, BA Smith, GD Hall, P. Harnden, P. Roberts, PJ Selby, LK Trejdosiewicz, J. Southgate: Uroplakin Gene Expression by Normal and Neoplastic Human Urothelium. In: American Journal of Pathology , 1998; Volume 153 (Issue 6): pp. 1957-1967. doi: 10.1016 / S0002-9440 (10) 65709-4 .
  11. ↑ G. Wang, L. Xiao, M. Zhang, AM Kamat, A. Siefker-Radtke, CP Dinney, B. Czerniak, CC Guo: Small cell carcinoma of the urinary bladder: a clinicopathological and immunohistochemical analysis of 81 cases. In: Human Pathology , 2018; Volume 79: pp. 57-65. doi: 10.1016 / j.humpath.2018.05.005 .