SIGNIFICANCE OF UROMODULIN IN THE DEVELOPMENT AND PROGRESSION OF CHRONIC KIDNEY DISEASE.
Keywords:
Uromodulin, Tamm-Horsfall protein, Chronic kidney disease, genetic, urinaryAbstract
Uromodulin (Tamm-Horsfall protein) is produced in the kidney by cells of the thick ascending limb and distal tubule. Recent genetic studies suggest a role of uromodulin in chronic kidney disease. Mutations in the UMOD gene cause uromodulin storage disease. They code for amino acid substitutions that lead to misfolding of the molecule and its retention in the endoplasmic reticulum. Single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease. Chronic kidney disease is associated with higher serum levels of uromodulin. From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease.
References
Tamm I, Horsfall FL. Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med 1950;74(1):106–108
Tamm I, Horsfall FL. A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. J Exp Med 1952;95(1):71–97. doi: 10.1084/jem.95.1.71
Muchmore AV, Decker JM. Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women. Science 1985;229(4712):479–481. doi:10.1126/science.2409603
Pennica D,Kohr WJ, Kuang WJ et al. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science 1987;236(4797):83–88. doi: 10.1126/science.3453112
Micanovic R, LaFavers K, Garimella PS et al. Uromodulin (Tamm-Horsfall protein): guardian of urinary and systemic homeostasis. Nephrol Dial Transplant 2019;Jan 14. doi: 10.1093/ndt/gfy394
El-Achkar TM, Wu XR. Uromodulin in kidney injury: an instigator, bystander or protector? Am J Kidney Dis 2012;59(3):452–461. doi: 10.1053/j.ajkd.2011.10.054
Serafini-Cessi F, Malagolini N, Cavallone D. Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 2003;42(4):658–676. doi: 10.1016/S0272-6386(03)00829-1
Serafini-Cessi F, Malagolini N, Hoops TC, Rindler MJ.Biosynthesis and oligosaccharide processing of human TammHorsfall glycoprotein permanently expressed in HeLa cells. Biochem Biophys Res Commun 1993;194(2):784–790. doi: 10.1006/bbrc.1993.1890
Bachmann S, Koeppen-Hagemann I, Kriz W. Ultrastructurallocalization of Tamm-Horsfall glycoprotein (THP) in rat kidney asrevealed by protein A-gold immunocytochemistry. Histochemistry 1985;83(6):531–538. doi: 10.1007/bf00492456
Hoyer JR,Sisson SP, Vernier RL. Tamm-Horsfall glycoprotein: ultrastructural immunoperoxidase localization in rat kidney. Lab Invest 1979;41(2):168–173
Rampoldi L, Scolari F, Amoroso A et al. The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease. Kidney Int 2011;80(4):338–347. doi: 10.1038/ki.2011.134
Bokhove M, Nishimura K, Brunati M et al. A structured interdomain linker directs self-polymerization of human uromodulin. Proc Natl Acad Sci USA 2016;113(6):1552–1557. doi: 10.1073/pnas.1519803113
Micanovic R, Khan S, Janosevic D et al. Tamm–Horsfall protein regulates mononuclear phagocytes in the kidney. J Am Soc Nephrol 2018;29(3):841–856. doi: 10.1681/asn.2017040409
Ferguson MA, Williams AF. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev. bi.57.070188.001441
Rindler MJ, Naik SS, Hoops TC, Peraldi MN. Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositollinked membrane protein. J Biol Chem 1990;265(34):20784–20789
Santambrogio S, Cattaneo A, Bernascone I et al. Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage. Biochem Biophys Res Commun 2008;370(3):410–413. doi: 10.1016/j.bbrc.2008.03.099
van Rooijen JJ, Voskamp AF, Kamerling JP et al. Glycosylation sites and site-specific glycosylation in human Tamm–Horsfall glycoprotein. Glycobiology 1999;9(1):21–30. doi: 10.1093/glycob/9.1.21
Benting JH, Rietveld AG, Simons K. N-Glycans mediatethe apical sorting of a GPI-anchored, raft-associated protein in Madin-Darby canine kidney cells. J Cell Biol 1999;146:313–320. doi: 10.1083/jcb.146.2.313
Brown DA, Rose JK. Sorting of GPI-anchored proteins to glycolipidenriched membrane subdomains during transport to the apical cell surface. Cell 1992;68:533–544
Schaeffer C, Santambrogio S, Perucca S et al. Analysis of uromodulin polymerization provides new insights into the mechanisms regulating ZP domain-mediated protein assembly. Mol Biol Cell 2009;20(2):589–599. doi: 10.1091/mbc.e08-08-0876
Brunati M, Perucca S, Han L et al. The serine protease hepsin mediates urinary secretion and polymerisation of zona pellucida domain protein uromodulin. Elife 2015;4:e08887. doi: 10.7554/eLife.08887
Santambrogio S, Cattaneo A, Bernascone I et al. Urinary uromodulin carries an intact ZP domain generated by a conserved C-terminal proteolytic cleavage. Biochem Biophys Res Commun 2008;370(3):410–413. doi: 10.1016/j.bbrc.2008.03.099
Wiggins RC. Uromucoid (Tamm–Horsfall glycoprotein) forms different polymeric arrangements on a filter surface under different physicochemical conditions. Clin Chim Acta 1987;162(3):329–340. doi: 10.1016/0009-8981(87)90052-0
Cavallone D, Malagolini N, Monti A et al. Variation of high mannose chains of Tamm–Horsfall glycoprotein confers differential binding to type 1-fimbriated Escherichia coli. J Biol Chem 2004;279(1):216–222. doi: 10.1074/jbc.m308821200
Wilburn DB, Swanson WJ. The «ZP domain» is not one, but likely two independent domains. Mol Reprod Dev 2017;84(4):284– 285. doi: 10.1002/mrd.22781
Easton RL, Patankar MS, Lattanzio FA et al. Structural analysis of murine zona pellucida glycans. Evidence for the expression of core 2-type O-glycans and the Sd(a) antigen. J Biol Chem 2000;275(11):7731–7742. doi: 10.1074/jbc.275.11.7731
Jennings P, Aydin S, Kotanko P. Membrane targeting and secretion of mutant uromodulin in familial juvenile hyperuricemic nephropathy. J Am Soc Nephrol 2007;18(1):264–273. doi: 10.1681/ASN.2006020158
Horton JK, Davies M, Woodhead JS, Weeks I. A new andrapid immunochemiluminometric assay for the measurement of Tamm-Horsfall glycoprotein. Clin Chim Acta 1988;174(2):225–237.doi: 10.1016/0009-8981(88)90389-0
Dawnay AB, Thornley C, Cattell WR. An improved radioimmunoassay for urinary Tamm-Horsfall glycoprotein. Investigation and resolution of factors affecting its quantification. Biochem J1982;206(3):461–465. doi: 10.1042/bj2060461
Lynn KL, Marshall RD. Excretion of Tamm-Horsfall glycoprotein in renal disease. Clin Nephrol 1984;22(5):253–257
El-Achkar TM, McCracken R, Rauchman et al. TammHorsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism. Am J Physiol Renal Physiol 2011;300(4):F999–F1007. doi: 10.1152/ ajprenal.00621.2010
Prajczer S, Heidenreich U, Pfaller W et al. Evidence for a role of uromodulin in chronic kidney disease progression. Nephrol Dial Transplant 2010;25(6):1896–1903. doi: 10.1093/ndt/gfp748
Smirnov AV, Khasun M, Kayukov IG et al. Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patientswith glomerulopathies. Ter Arkh 2018;90(6):41–44. (In Russ.) doi:10.26442/terarkh201890641-47
Bichler KH, Ideler V, Harzmann R. Uromucoid excretionin normal individuals and stone formers. Curr Probl Clin Biochem1979; 9:309–324
Glauser A, Hochreiter W, Jaeger P, Hess B. Determinants of urinary excretion of Tamm-Horsfall protein in non-selected kidney stone formers and healthy subjects. Nephrol Dial Transplant 2000;15(10):1580–1587. doi: 10.1093/ndt/15.10.1580
Thornley C, Dawnay A, Cattell WR. Human Tamm-Horsfall glycoprotein: urinary and plasma levels in normal subjects and patients with renal disease determined by a fully validated radioimmunoassay. Clin Sci (Lond) 1985;68(5):529–535. doi: 10.1042/ cs0680529
Romero MC, Zanaro N, Gonzalez L et al. Tamm-Horsfall protein excretion to predict the onset of renal insufficiency. Clin Biochem 2002;35(1):65–68. doi:10.1016/s0009-9120(02)00274-6
Ollier-Hartmann MP, Pouget-Abadie C, Bouillie J, Hartmann L. Variations of urinary Tamm-Horsfall protein in humansduring the first thirty years of life. Nephron 1984;38(3):163–166.doi: 10.1159/000183300
Duława J, Kokot F, Kokot M, Pander HJ. Urinary excretion of Tamm-Horsfall protein in normotensive and hypertensive elderly patients. J Hum Hypertens 1998;12(9):635–637. doi: 10.1038/ sj.jhh.1000680
Ying WZ, Sanders PW. Dietary salt regulates expression of TammHorsfall glycoprotein in rats. Kidney Int 1998;54(4):1150–1156. doi: 10.1046/j.1523-1755.1998.00117.x
Grant AM, Neuberger A. The turnover rate of rabbit urinaryTamm-Horsfall glycoprotein. Biochem J 1973;136(3):659–668.doi: 10.1042/bj1360659
van Rooijen JJ, Kamerling JP, Vliegenthart JF. Sulfateddi-, tri- and tetraantennary N-glycans in human Tamm-Horsfallglycoprotein. Eur J Biochem 1998;256(2):471–487. doi:10.1046/j.1432-1327.1998.2560471.x
Vyletal P, Bleyer AJ, Kmoch S. Uromodulin biology and pathophysiology–an update. Kidney Blood Press Res2010;33(6):456–475. doi: 10.1159/000321013
Pak J, Pu Y, Zhang ZT et al. Tamm-Horsfall protein binds totype 1 fimbriated Escherichia coli and prevents E. coli from bindingto uroplakin Ia and Ib receptors. J Biol Chem 2001;276:9924–9930.doi: 10.1074/jbc.m008610200
Raffi HS, Bates JM, Laszik Z, Kumar S. Tamm-Horsfallprotein acts as a general host-defense factor against bacterial cystitis. Am J Nephrol 2005;25(6):570–578. doi: 10.1159/000088990
Bates JM, Raffi HM, Prasadan K et al. Tamm-Horsfallprotein knockout mice are more prone to urinary tract infection: rapid communication. Kidney Int 2004;65(3):791–797. doi:0.1111/j.1523-1755.2004.00452.x
Mo L, Huang HY, Zhu XH et al. Tamm-Horsfall protein is a critical renal defense factor protecting against calcium oxalate crystal formation. Kidney Int 2004;66(3):1159–1166. doi:10.1111/j.1523-1755.2004.00867.x
Gresh L, Fische E, Reimann A et al. A transcriptional network in polycystic kidney disease. EMBO J 2004;23(7):1657–1668. doi: 10.1038/sj.emboj.7600160
Bingham C, Ellard S, van’t Hoff WG et al. Atypical familial uvenile hyperuricemic nephropathy associated with a hepatocytenuclear factor-1beta gene mutation. Kidney Int 2003;63(5):1645–1651. doi: 10.1046/j.1523-1755.2003.00903.x
Torffvit O, Melander O, Hultén UL. Urinary excretion rate ofTammHorsfall protein is related to salt intake in humans. Nephron Physiol 2004;97(1):31–36. doi: 10.1159/000077600
Bachmann S, Dawnay AB, Bouby N, Bankir L. TammHorsfall protein excretion during chronic alterations in urinary concentration and protein intake in the rat. Ren Physiol Biochem1991;14(6):236–245. doi: 10.1159/000173411
Guidi E, Giglioni A, Cozzi MG, Minetti EE. Which urinary proteins are decreased after angiotensin converting–enzyme inhibition? Ren Fail 1998;20(2):243–248. doi:10.3109/08860229809045108
Cairns HS, Dawnay A, Woolfson RG, Unwin RJ. Evaluation of therapy for cast nephropathy: failure of colchicine to alter urinary Tamm Horsfall glycoprotein excretion in normal subjects.Exp Nephrol 1994;2(4):257–258
J.A. Rizaev, I.R.Agababyan, Y.A.Ismoilova ACTIVITIES OF CLINICS SPECIALIZING IN THE TREATMENT OF PATIENTS WITH CHRONIC HEART DISEASE IN THE WORLD (REFERENCES). Journal of Biomedicine and Practice. 2021, vol. 6, issue 6, pp. 184-191
Alimdjanovich, Rizayev Jasur, Agababyan Irina Rubenovna, and Ismoilova Yulduz Abduvokhidovna. "SPECIALIZED CENTER FOR THE PATIENTS WITH CHRONIC HEART FAILURE-EXTENSION OF LIFE." Вопросы науки и образования 22 (147) (2021): 14-24.
Rizaev A. Jhasur, Makhmonov S. Lutfulla, Gadaev G. Abdugaffor, Turakulov I. Rustam. Assessment of external factors involved in prediction of iron deficiency anemia associated with Helicobacter Pylori. Journal of Biomedicine and Practice. 2022, vol.7, issue 4, pp. 436-446
