nach oben

Pediatric Nephrology

Erschienen in:

26.04.2016 | Review

Role of renal urothelium in the development and progression of kidney disease

verfasst von: Ashley R. Carpenter, Kirk M. McHugh

Erschienen in: Pediatric Nephrology | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Abstract

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb ^−/−) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1b ^RFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

(2012) U.S. Renal data system, USRDS 2012 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National institutes of health, national institute of diabetes and digestive and kidney diseases, Bethesda, MD, 2012

(2007) U.S. Renal data system, USRDS 2007 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National institutes of health, national institute of diabetes and digestive and kidney diseases, Bethesda, MD

Wong CJ, Moxey-Mims M, Jerry-Fluker J, Warady BA, Furth SL (2012) CKiD (CKD in children) prospective cohort study: a review of current findings. Am J Kidney Dis 60:1002–1011CrossRefPubMedPubMedCentral

Roth KS, Carter WH Jr, Chan JC (2001) Obstructive nephropathy in children: long-term progression after relief of posterior urethral valve. Pediatrics 107:1004–1010CrossRefPubMed

Ingraham SE, Saha M, Carpenter AR, Robinson M, Ismail I, Singh S, Hains D, Robinson ML, Hirselj DA, Koff SA, Bates CM, McHugh KM (2010) Pathogenesis of renal injury in the megabladder mouse: a genetic model of congenital obstructive nephropathy. Pediatr Res 68:500–507CrossRefPubMedPubMedCentral

Singh S, Robinson M, Nahi F, Coley B, Robinson ML, Bates CM, Kornacker K, McHugh KM (2007) Identification of a unique transgenic mouse line that develops megabladder, obstructive uropathy, and renal dysfunction. J Am Soc Nephrol 18:461–471CrossRefPubMed

Aboushwareb T, Zhou G, Deng FM, Turner C, Andersson KE, Tar M, Zhao W, Melman A, D’Agostino R Jr, Sun TT, Christ GJ (2009) Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice. Neurourol Urodyn 28:1028–1033CrossRefPubMedPubMedCentral

Zhou G, Mo WJ, Sebbel P, Min G, Neubert TA, Glockshuber R, Wu XR, Sun TT, Kong XP (2001) Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci 114:4095–4103PubMed

Hu P, Deng FM, Liang FX, Hu CM, Auerbach AB, Shapiro E, Wu XR, Kachar B, Sun TT (2000) Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux. J Cell Biol 151:961–972CrossRefPubMedPubMedCentral

10.

Kong XT, Deng FM, Hu P, Liang FX, Zhou G, Auerbach AB, Genieser N, Nelson PK, Robbins ES, Shapiro E, Kachar B, Sun TT (2004) Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases. J Cell Biol 167:1195–1204CrossRefPubMedPubMedCentral

11.

Romih R, Korosec P, De Mello W Jr, Jezernik K (2005) Differentiation of epithelial cells in the urinary tract. Cell Tissue Res 320:259–268CrossRefPubMed

12.

Carpenter AR, Becknell B, Ching CB, Cuaresma EJ, Chen X, Hains DS, McHugh KM (2016) Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis. Kidney Int 89:612–624CrossRefPubMed

13.

Wu XR, Lin JH, Walz T, Haner M, Yu J, Aebi U, Sun TT (1994) Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins. J Biol Chem 269:13716–13724PubMed

14.

Garcia-Espana A, Chung PJ, Zhao X, Lee A, Pellicer A, Yu J, Sun TT, Desalle R (2006) Origin of the tetraspanin uroplakins and their co- evolution with associated proteins: implications for uroplakin structure and function. Mol Phylogenet Evol 41:355–367CrossRefPubMed

15.

Deng FM, Liang FX, Tu L, Resing KA, Hu P, Supino M, Hu CC, Zhou G, Ding M, Kreibich G, Sun TT (2002) Uroplakin IIIb, a urothelial differentiation marker, dimerizes with uroplakin Ib as an early step of urothelial plaque assembly. J Cell Biol 159:685–694CrossRefPubMedPubMedCentral

16.

Yu J, Lin JH, Wu XR, Sun TT (1994) Uroplakins Ia and Ib, two major differentiation products of bladder epithelium, belong to a family of four transmembrane domain (4TM) proteins. J Cell Biol 125:171–182CrossRefPubMed

17.

Wu XR, Medina JJ, Sun TT (1995) Selective interactions of UPIa and UPIb, two members of the transmembrane 4 superfamily, with distinct single transmembrane-domained proteins in differentiated urothelial cells. J Biol Chem 270:29752–29759CrossRefPubMed

18.

Liang FX, Riedel I, Deng FM, Zhou G, Xu C, Wu XR, Kong XP, Moll R, Sun TT (2001) Organization of uroplakin subunits: transmembrane topology, pair formation and plaque composition. Biochem J 355:13–18CrossRefPubMedPubMedCentral

19.

Hu CC, Liang FX, Zhou G, Tu L, Tang CH, Zhou J, Kreibich G, Sun TT (2005) Assembly of urothelial plaques: tetraspanin function in membrane protein trafficking. Mol Biol Cell 16:3937–3950CrossRefPubMedPubMedCentral

20.

Min G, Stolz M, Zhou G, Liang F, Sebbel P, Stoffler D, Glockshuber R, Sun TT, Aebi U, Kong XP (2002) Localization of uroplakin Ia, the urothelial receptor for bacterial adhesin FimH, on the six inner domains of the 16 nm urothelial plaque particle. J Mol Biol 317:697–706CrossRefPubMed

21.

Sakakibara K, Sato K, Yoshino K, Oshiro N, Hirahara S, Mahbub Hasan AK, Iwasaki T, Ueda Y, Iwao Y, Yonezawa K, Fukami Y (2005) Molecular identification and characterization of Xenopus egg uroplakin III, an egg raft-associated transmembrane protein that is tyrosine-phosphorylated upon fertilization. J Biol Chem 280:15029–15037CrossRefPubMed

22.

Jenkins D, Bitner-Glindzicz M, Malcolm S, Hu CC, Allison J, Winyard PJ, Gullett AM, Thomas DF, Belk RA, Feather SA, Sun TT, Woolf AS (2005) De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure. J Am Soc Nephrol 16:2141–2149CrossRefPubMed

23.

Wang H, Min G, Glockshuber R, Sun TT, Kong XP (2009) Uropathogenic E. coli adhesin-induced host cell receptor conformational changes: implications in transmembrane signaling transduction. J Mol Biol 392:352–361CrossRefPubMedPubMedCentral

24.

Thumbikat P, Berry RE, Zhou G, Billips BK, Yaggie RE, Zaichuk T, Sun TT, Schaeffer AJ, Klumpp DJ (2009) Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathog 5:e1000415CrossRefPubMedPubMedCentral

25.

Tu L, Kong XP, Sun TT, Kreibich G (2006) Integrity of all four transmembrane domains of the tetraspanin uroplakin Ib is required for its exit from the ER. J Cell Sci 119:5077–5086CrossRefPubMed

26.

Becknell B, Carpenter AR, Allen JL, Wilhide ME, Ingraham SE, Hains DS, McHugh KM (2013) Molecular basis of renal adaptation in a murine model of congenital obstructive nephropathy. PLoS One 8:e72762CrossRefPubMedPubMedCentral

27.

Vinsonneau C, Girshovich A, M’Rad MB, Perez J, Mesnard L, Vandermersch S, Placier S, Letavernier E, Baud L, Haymann JP (2010) Intrarenal urothelium proliferation: an unexpected early event following ischemic injury. Am J Physiol Renal Pysiol 299:F479–F486CrossRef

28.

Girshovich A, Vinsonneau C, Perez J, Vandermeersch S, Verpont MC, Placier S, Jouanneau C, Letavernier E, Baud L, Haymann JP (2012) Ureteral obstruction promotes proliferation and differentiation of the renal urothelium into a bladder-like phenotype. Kidney Int 82:428–435CrossRefPubMed

29.

Wood MW, Breitschwerdt EB, Nordone SK, Linder KE, Gookin JL (2012) Uropathogenic E. coli promote a paracellular urothelial barrier defect characterized by altered tight junction integrity, epithelial cell sloughing and cytokine release. J Comp Pathol 147:11–19CrossRefPubMed

30.

Shin K, Lee J, Guo N, Kim J, Lim A, Qu L, Mysorekar IU, Beachy PA (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472:110–114CrossRefPubMedPubMedCentral

31.

McHugh KM (2014) Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation. Pediatr Nephrol 29:645–650CrossRefPubMed

32.

Becknell B, Mohamed AZ, Li B, Wilhide ME, Ingraham SE (2015) Urine stasis predisposes to urinary tract infection by an opportunistic uropathogen in the megabladder (Mgb) mouse. PLoS One 10:e0139077CrossRefPubMedPubMedCentral

33.

McMahon AP, Aronow BJ, Davidson DR, Davies JA, Gaido KW, Grimmond S, Lessard JL, Little MH, Potter SS, Wilder EL, Zhang P, project G (2008) GUDMAP: the genitourinary developmental molecular anatomy project. J Am Soc Nephrol 19:667–671CrossRefPubMed

34.

Mauney JR, Ramachandran A, Yu RN, Daley GQ, Adam RM, Estrada CR (2010) All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms. PLoS One 5:e11513CrossRefPubMedPubMedCentral

35.

Adachi W, Okubo K, Kinoshita S (2000) Human uroplakin Ib in ocular surface epithelium. Invest Ophthalmol Vis Sci 41:2900–2905PubMed

36.

Harding SD, Armit C, Armstrong J, Brennan J, Cheng Y, Haggarty B, Houghton D, Lloyd-MacGilp S, Pi X, Roochun Y, Sharghi M, Tindal C, McMahon AP, Gottesman B, Little MH, Georgas K, Aronow BJ, Potter SS, Brunskill EW, Southard-Smith EM, Mendelsohn C, Baldock RA, Davies JA, Davidson D (2011) The GUDMAP database--an online resource for genitourinary research. Development 138:2845–2853CrossRefPubMedPubMedCentral

37.

Smith CM, Finger JH, Hayamizu TF, McCright IJ, Xu J, Berghout J, Campbell J, Corbani LE, Forthofer KL, Frost PJ, Miers D, Shaw DR, Stone KR, Eppig JT, Kadin JA, Richardson JE, Ringwald M (2014) The mouse gene expression database (GXD): 2014 update. Nucleic Acids Res 42:D818–D824CrossRefPubMed

38.

Thumbikat P, Berry RE, Schaeffer AJ, Klumpp DJ (2009) Differentiation- induced uroplakin III expression promotes urothelial cell death in response to uropathogenic E. coli. Microbes Infect 11:57–65CrossRefPubMed

39.

Ogawa K, Johansson SL, Cohen SM (1999) Immunohistochemical analysis of uroplakins, urothelial specific proteins, in ovarian Brenner tumors, normal tissues, and benign and neoplastic lesions of the female genital tract. Am J Pathol 155:1047–1050CrossRefPubMedPubMedCentral

40.

Cheng L, Cheville JC, Neumann RM, Bostwick DG (1999) Natural history of urothelial dysplasia of the bladder. Am J Surg Pathol 23:443–447CrossRefPubMed

41.

Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30CrossRefPubMed

42.

Raman JD, Ng CK, Boorjian SA, Vaughan ED Jr, Sosa RE, Scherr DS (2005) Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology. BJU Int 96:1031–1035CrossRefPubMed

43.

Chow WH, Lindblad P, Gridley G, Nyren O, McLaughlin JK, Linet MS, Pennello GA, Adami HO, Fraumeni JF Jr (1997) Risk of urinary tract cancers following kidney or ureter stones. J Natl Cancer Inst 89:1453–1457CrossRefPubMed

44.

Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, Chen JT, Cope E, Gipson D, He K, Herman W, Heung M, Hirth RA, Jacobsen SS, Kalantar-Zadeh K, Kovesdy CP, Leichtman AB, Lu Y, Molnar MZ, Morgenstern H, Nallamothu B, O’Hare AM, Pisoni R, Plattner B, Port FK, Rao P, Rhee CM, Schaubel DE, Selewski DT, Shahinian V, Sim JJ, Song P, Streja E, Kurella Tamura M, Tentori F, Eggers PW, Agodoa LY, Abbott KC (2015) US renal data system 2014 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 65:A7CrossRef

Titel: Role of renal urothelium in the development and progression of kidney disease
verfasst von: Ashley R. Carpenter
Kirk M. McHugh
Publikationsdatum: 26.04.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 4/2017
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-016-3385-6

Neu im Fachgebiet Pädiatrie

18.04.2024 | Spinale Muskelatrophien | Nachrichten

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Role of renal urothelium in the development and progression of kidney disease

Abstract

Neu im Fachgebiet Pädiatrie

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Zunahme von Geschlechtsinkongruenz und -dysphorie registriert

Intrakapsuläre Tonsillektomie gewinnt an Boden

Update Pädiatrie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2017

Occurrence of neutrophil dysplasia in the course of severe nephrotic syndrome in a 12-year-old boy on immunosuppressive therapy: Questions

Plasma-cell-rich infiltrates in paediatric renal transplant biopsies are associated with increased risk of renal allograft failure

M-type phospholipase A2 receptor (PLA2R) glomerular staining in pediatric idiopathic membranous nephropathy

Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD

Fetal first trimester growth is not associated with kidney outcomes in childhood

Poor outcomes for children on the wait list at low-volume kidney transplant centers in the United States

Neu im Fachgebiet Pädiatrie

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Zunahme von Geschlechtsinkongruenz und -dysphorie registriert

Intrakapsuläre Tonsillektomie gewinnt an Boden

Update Pädiatrie