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01-09-2013 | Review

Angiogenesis and autosomal dominant polycystic kidney disease

Authors: Jennifer L. Huang, Adrian S. Woolf, David A. Long

Published in: Pediatric Nephrology | Issue 9/2013

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of multiple cysts that in many cases result in end-stage renal disease. Current strategies to reduce cyst progression in ADPKD focus on modulating cell turnover, fluid secretion, and vasopressin signalling; but an alternative approach may be to target pathways providing “general support” for cyst growth, such as surrounding blood vessels. This could be achieved by altering the expression of growth factors involved in vascular network formation, such as the vascular endothelial growth factor (VEGF) and angiopoietin families. We highlight the evidence that blood vessels and vascular growth factors play a role in ADPKD progression. Recent experiments manipulating VEGF in ADPKD are described, and we discuss how alternative strategies to manipulate angiogenesis may be used in the future as a novel treatment for ADPKD.

Harris PC, Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60:321–327PubMedCrossRef

Mekahli D, Woolf AS, Bockenhauer D (2010) Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms. Pediatr Nephrol 25:2275–2282PubMedCrossRef

Wilson PD, Goilav B (2007) Cystic disease of the kidney. Annu Rev Pathol 2:341–368PubMedCrossRef

Masyuk TV, Masyuk AI, Torres VE, Harris PC, Larusso NF (2007) Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3’,5-cyclic monophosphate. Gastroenterology 132:1104–1116PubMedCrossRef

Gattone VH, Wang X, Harris PC, Torres VC (2003) Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 9:1323–1326PubMedCrossRef

Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, Weimbs T (2006) The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A 103:5466–5471PubMedCrossRef

Chang MY, Ong AC (2012) Mechanism-based therapeutics for autosomal dominant polycystic kidney disease: recent progress and future prospects. Nephron Clin Pract 120:c25–c34PubMedCrossRef

Nguyen AN, Wallace DP, Blanco G (2007) Ouabain binds with high affinity to the Na, K-ATPase in human polycystic kidney cells and induces extracellular signal-regulated kinase activation and proliferation. J Am Soc Nephrol 18:46–57PubMedCrossRef

Bello-Reuss E, Holubec K, Rajaraman S (2001) Angiogenesis in autosomal dominant polycystic kidney disease. Kidney Int 60:37–45PubMedCrossRef

10.

Wei W, Popov V, Walocha JA, Wen J, Bello-Reuss E (2006) Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion case study. Kidney Int 70:1261–1268PubMedCrossRef

11.

Long DA, Norman JT, Fine LG (2012) Restoring the renal microvasculature to treat chronic kidney disease. Nat Rev Nephrol 9:244–250CrossRef

12.

Kim K, Drummond I, Ibraghimov-Beskrovnaya O, Klinger K, Arnaout MA (2000) Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci U S A 97:1731–1736PubMedCrossRef

13.

Ong AC, Ward CJ, Butler RJ, Biddolph S, Bowker C, Torra R, Pei Y, Harris PC (1999) Coordinate expression of the autosomal dominant polycystic kidney disease proteins, polycystin-2 and polycystin-1, in normal and cystic tissue. Am J Pathol 154:1721–1729PubMedCrossRef

14.

Torres VE, Cai Y, Chen X, Wu GQ, Geng L, Cleghorn KA, Johnson CM, Somlo S (2001) Vascular expression of polycystin-2. J Am Soc Nephrol 12:1–9PubMed

15.

Nauli SM, Kawanabe Y, Kaminski JJ, Pearce WJ, Ingber DE, Zhou J (2008) Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation 117:1161–1171PubMedCrossRef

16.

AbouAlaiwi WA, Takahashi M, Mell BR, Jones TJ, Ratnam S, Kolb RJ, Nauli SM (2009) Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signalling cascades. Circ Res 104:860–869PubMedCrossRef

17.

Hassane S, Claij N, Jodar M, Dedman A, Lauritzen I, Duprat F, Koendermann JS, van der Wal A, Breuning MH, de Heer E, Honore E, DeRuiter MC, Peters DJ (2011) Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension. Lab Investig 91:24–32PubMedCrossRef

18.

Lohela M, Bry M, Tammela T, Alitalo K (2009) VEGFs and receptors involved in angiogenesis versus lymphiangiogenesis. Curr Opin Cell Biol 21:154–165PubMedCrossRef

19.

Woolf AS, Gnudi L, Long DA (2009) Roles of angiopoietins in kidney development and disease. J Am Soc Nephrol 20:239–244PubMedCrossRef

20.

Ferrara N (2010) Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 21:687–690PubMedCrossRef

21.

Harper SJ, Bates DO (2008) VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer 8:880–887PubMedCrossRef

22.

Kim KT, Choi HH, Steinmetz MO, Maco B, Kammerer RA, Ahn SY, Kim HZ, Lee GM, Koh GY (2005) Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2. J Biol Chem 280:20126–20131PubMedCrossRef

23.

Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulous N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60PubMedCrossRef

24.

Felcht M, Luck R, Schering A, Seidel P, Srivastava K, Hu J, Bartol A, Kienast Y, Vettel C, Loos EK, Kutschera S, Bartels S, Appak S, Besemfelder E, Terhardt D, Chavakis E, Wieland T, Klein C, Thomas M, Uemura A, Goerdt S, Augustin HG (2012) Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J Clin Invest 122:1991–2005PubMedCrossRef

25.

Stringer KD, Komers R, Osman SA, Oyama TT, Lindsley JN, Anderson S (2005) Gender hormones and the progression of experimental polycystic kidney disease. Kidney Int 68:1729–1739PubMedCrossRef

26.

Brown JH, Bihoreau MT, Hoffmann S, Kranzlin B, Tychinskaya I, Obermuller N, Podlich D, Boehn SN, Kaisaki PJ, Megel N, Danoy P, Copley RR, Broxholme J, Witzgall R, Lathrop M, Gretz N, Gauguier D (2005) Missense mutation in sterile alpha motif of novel protein SamCystin is associated with polycystic kidney disease in (cy/+) rat. J Am Soc Nephrol 16:3517–3526PubMedCrossRef

27.

Song X, Di Giovanni V, He N, Wang K, Ingram A, Rosenblum ND, Pei Y (2009) Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks. Hum Mol Genet 18:2328–2343PubMedCrossRef

28.

Tao Y, Kim J, Yin Y, Zafar I, Falk S, He Z, Faubel S, Schrier RW, Edelsterin CL (2007) VEGF receptor inhibition slows the progression of polycystic kidney disease. Kidney Int 72:1358–1366PubMedCrossRef

29.

Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613PubMed

30.

Bernhardt WM, Wiesener MS, Weidmann A, Schmitt R, Weichert W, Lechler P, Campean V, Ong AC, Willam C, Gretz N, Eckardt KU (2007) Involvement of hypoxia-inducible transcription factors in polycystic kidney disease. Am J Pathol 170:830–842PubMedCrossRef

31.

Esteban MA, Harten SK, Tran MG, Maxwell PH (2006) Formation of primary cilia in the renal epithelium is regulated by the von Hippel-Lindau tumor suppressor protein. J Am Soc Nephrol 17:1801–1806PubMedCrossRef

32.

Rankin EB, Tomaszewski JE, Haase VH (2006) Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res 66:2576–2583PubMedCrossRef

33.

Fu L, Wang G, Shevchuk MM, Nanus DM, Gudas LJ (2011) Generation of a mouse model of von Hippel-Lindau kidney disease leading to renal cancers by expression of a constitutively active mutant of HIF1α. Cancer Res 71:6848–6856PubMedCrossRef

34.

Schietke RE, Hackenbeck T, Tran M, Günther R, Klanke B, Warnecke CL, Knaup KX, Shukla D, Rosenberger C, Koesters R, Bachmann S, Betz P, Schley G, Schödel J, Willam C, Winkler T, Amann K, Eckardt KU, Maxwell P, Wiesener MS (2012) Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts. PLoS One 7:e31034PubMedCrossRef

35.

Madsen K, Marcussen N, Pedersen M, Kjaersgaard G, Facemire C, Coffman TM, Jensen BL (2010) Angiotensin II promotes development of the renal microcirculation through AT1 receptors. J Am Soc Nephrol 21:448–459PubMedCrossRef

36.

Rizkalla B, Forbes JM, Cooper ME, Cao Z (2003) Increased renal vascular endothelial growth factor and angiopoietins by angiotensin II infusion is mediated by both AT1 and AT2 receptors. J Am Soc Nephrol 14:3061–3071PubMedCrossRef

37.

Loghman-Adham M, Soto CE, Inagami T, Cassis L (2004) The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Ren Physiol 287:F775–F788CrossRef

38.

dela Paz NG, Walshe TE, Leach LL, Saint-Geniez M, D’Amore PA (2012) Role of shear-stress-induced VEGF expression in endothelial cell survival. J Cell Sci 125:831–843CrossRef

39.

Goettsch W, Gryczka C, Korff T, Ernst E, Goettsch C, Seebach J, Schnittler HJ, Augustin HG, Morawietz H (2008) Flow-dependent regulation of angiopoietin-2. J Cell Physiol 214:491–503PubMedCrossRef

40.

Reed BY, Masoumi A, Elhassan E, McFann K, Cadnapaphornchai MA, Maahs DM, Snell-Bergeon JK, Schrier RW (2011) Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease. Kidney Int 79:128–134PubMedCrossRef

41.

Kanellis J, Fraser S, Katerelos M, Power DA (2000) Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells. Am J Physiol Ren Physiol 278:F905–F915

42.

Villegas G, Lange-Sperandio B, Tufro A (2005) Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells. Kidney Int 67:449–457PubMedCrossRef

43.

Hakroush S, Moeller MJ, Theilig F, Kaissling B, Sijmonsma TP, Jugold M, Akeson AL, Traykova-Brauch M, Hosser H, Hahnel B, Grone HJ, Koesters R, Kriz W (2009) Effects of increased renal tubular vascular endothelial growth factor (VEGF) on fibrosis, cyst formation and glomerular disease. Am J Pathol 175:1883–1895PubMedCrossRef

44.

Rees KA, Singh H, Brindle NP (2007) The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines. Int J Oncol 31:893–897PubMed

45.

Makinde TO, Agrawal DK (2011) Increased expression of angiopoietins and Tie2 in the lungs of chronic asthmatic mice. Am J Respir Cell Mol Biol 44:384–393PubMedCrossRef

46.

Ramsden JD, Cocks HC, Shams M, Niijar S, Watkinson JC, Sheppard MC, Ahmed A, Eggo MC (2001) Tie-2 is expressed on thyroid follicular cells, is increased in goiter, and is regulated by thyrotropin through cyclic adenosine 3’5’-monophosphate. J Clin Endocrinol Metab 86:2709–2716PubMedCrossRef

47.

Wallace DP (2011) Cyclic AMP-mediated cyst expansion. Biochim Biophys Acta 1812:1291–1300PubMedCrossRef

48.

Teilmann SC, Christensen ST (2005) Localization of the angiopoietin receptors Tie-1 and Tie-2 on the primary cilia in the female reproductive organs. Cell Biol Int 29:340–346PubMedCrossRef

49.

Raina S, Honer M, Kramer SD, Liu Y, Wang X, Segerer S, Wuthrich RP, Serra AL (2011) Anti-VEGF antibody treatment accelerates polycystic kidney disease. Am J Physiol Ren Physiol 301:F773–F783CrossRef

50.

Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE (2008) VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 358:1129–1136PubMedCrossRef

51.

Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, Kalluri R (2003) Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 278:12605–12608PubMedCrossRef

52.

Amura CR, Brodsky KS, Groff R, Gattone VH, Voelkel NF, Doctor RB (2007) VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/-) mice. Am J Physiol Cell Physiol 293:C419–C428PubMedCrossRef

53.

Long DA, Price KL, Ioffe E, Gannon CM, Gnudi L, White KE, Yancopoulos GD, Rudge JS, Woolf AS (2008) Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injury. Kidney Int 74:300–309PubMedCrossRef

54.

Mu W, Long DA, Ouyang X, Agarwal A, Cruz PE, Roncal CA, Nakagawa T, Yu X, Hauswirth WW, Johnson RJ (2009) Angiostatin overexpression is associated with an improvement in chronic kidney injury by an anti-inflammatory mechanism. Am J Physiol Ren Physiol 296:F145–F152CrossRef

55.

Mellon MJ, Bae KH, Steding CE, Jimenez JA, Kao C, Gardner TA (2008) Suppression of renal cell carcinoma growth and metastasis with sustained antiangiogenic gene therapy. Hum Gene Ther 19:487–495PubMedCrossRef

56.

Carew JS, Esquvel JA 2nd, Espitia CM, Schultes CM, Milbaier M, Lewis JD, Janssen B, Giles FJ, Nawrocki ST (2012) ELR5104444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcimona. PLoS One 7:e31120PubMedCrossRef

57.

Yin KJ, Olsen K, Hamblin M, Zhang J, Schwendeman SP, Chen YE (2012) Vascular endothelial cell-specific microRNA-15a inhibits angiogenesis in himblimb ischemia. J Biol Chem 287:27055–27064PubMedCrossRef

58.

Chang MY, Parker E, El Nahas M, Haylor JL, Ong AC (2007) Endothelin B receptor blockade accelerates disease progression in a murine model of autosomal dominant polycystic kidney disease. J Am Soc Nephrol 18:560–569PubMedCrossRef

59.

Hocher B, Zart R, Schwarz A, Vogt V, Braun C, Thone-Reineke C, Braun N, Neumayer HH, Koppenhagen K, Bauer C, Rohmeiss P (1998) Renal endothelin system in polycystic kidney disease. J Am Soc Nephrol 9:1169–1177PubMed

60.

McCarter SD, Lai PF, Suen RS, Stewart DJ (2006) Regulation of endothelin-1 by angiopoietin-1: implications for inflammation. Exp Biol Med 231:985–991

61.

Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S (2009) Lymphatic vessels develop during tubulointerstitial fibrosis. Kidney Int 75:828–838PubMedCrossRef

Title: Angiogenesis and autosomal dominant polycystic kidney disease
Authors: Jennifer L. Huang
Adrian S. Woolf
David A. Long
Publication date: 01-09-2013
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 9/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-012-2305-7

At a glance: The STEP trials

Springer Medicine

Angiogenesis and autosomal dominant polycystic kidney disease

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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