A podocyte-based automated screening assay identifies protective small molecules

Journal of the American Society of Nephrology

Volumn 26, Issue 11, 2015, Pages 2741-2752

  Lee, Ha Won ^a   Khan, Samia Q ^a   Faridi, Mohd Hafeez ^a   Wei, Changli ^a   Tardi, Nicholas J ^a   Altintas, Mehmet M ^a   Elshabrawy, Hatem A ^a   Mangos, Steve ^a   Quick, Kevin L ^b   Sever, Sanja ^c   Reiser, Jochen ^a   Gupta, Vineet ^a  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

^b PERKINELMER INC   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; AGELASINE; ALSTERPAULLONE; ALTRENOGEST; AMFEBUTAMONE; ANTIMYCIN A1; APIGENIN; AUROTHIOGLUCOSE; BERBERINE; BETA1 INTEGRIN AGONIST; CLOXIQUINE; CRYOPROTECTIVE AGENT; CRYPTOTANSHINONE; DIOSMETIN; DOXAZOSIN MESYLATE; MUNDOSERONE; MUNDULONE ACETATE; NORGESTIMATE; PAPAVERINE; PROGUANIL; PYRINTEGRIN; QUINAMIDE ISOPROPYLIDENE; ROSEOLIC ACID; SALIGENIN; THIAZOVIVIN; THUJAPLICIN; TIOGUANINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ACTIN; BETA1 INTEGRIN; LIPOPOLYSACCHARIDE; PUROMYCIN AMINONUCLEOSIDE; QUINOLINOL DERIVATIVE; SULFONAMIDE;

ALBUMINURIA; ANIMAL CELL; ARTICLE; AUTOANALYSIS; CELL DAMAGE; CELL PROTECTION; CELL STRUCTURE; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DRUG DETERMINATION; DRUG SCREENING; GLOMERULUS; IN VITRO STUDY; IN VIVO STUDY; KIDNEY DISEASE; MOUSE; NONHUMAN; PODOCYTE; PODOCYTE CELL BASED PHENOTYPIC ASSAY; PRIORITY JOURNAL; PROTEINURIA; QUANTITATIVE ANALYSIS; RAT; ANIMAL; CELL MOTION; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; EPITHELIUM CELL; FOCAL ADHESION; HIGH THROUGHPUT SCREENING; METABOLISM; PATHOLOGY; PHENOTYPE;

ACTINS; ALBUMINURIA; ANIMALS; ANTIGENS, CD29; CELL MOVEMENT; EPITHELIAL CELLS; FOCAL ADHESIONS; HIGH-THROUGHPUT SCREENING ASSAYS; HYDROXYQUINOLINES; KIDNEY DISEASES; KIDNEY GLOMERULUS; LIPOPOLYSACCHARIDES; MICE; MICROSCOPY, CONFOCAL; PHENOTYPE; PODOCYTES; PROTEINURIA; PUROMYCIN AMINONUCLEOSIDE; RATS; SULFONAMIDES;

EID: 84938310769     PISSN: 10466673     EISSN: 15333450     Source Type: Journal    
DOI: 10.1681/ASN.2014090859     Document Type: Article

References (54)

1. Pavenstädt H, Kriz W, Kretzler M: Cell biology of the glomerular podocyte. Physiol Rev 83: 253-307, 2003
2. Faul C, Asanuma K, Yanagida-Asanuma E, Kim K, Mundel P: Actin up: Regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol 17: 428-437, 2007
3. Huber TB, Benzing T: The slit diaphragm: A signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens 14: 211-216, 2005
4. Reiser J, Sever S: Podocyte biology and pathogenesis of kidney disease. Annu Rev Med 64: 357-366, 2013
5. Wiggins RC: The spectrum of podocytopathies: A unifying view of glomerular diseases. Kidney Int 71: 1205-1214, 2007
6. Mathieson PW: The podocyte as a target for therapies-new and old. Nat Rev Nephrol 8: 52-56, 2012
7. Reiser J, Gupta V, Kistler AD: Toward the development of podocytespecific drugs. Kidney Int 77: 662-668, 2010
8. Faul C, DonnellyM, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P: The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14: 931-938, 2008
9. Mundel P, Reiser J, Zñiga Mejía Borja A, Pavenstädt H, Davidson GR, Kriz W, Zeller R: Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalizedmouse podocyte cell lines. Exp Cell Res 236: 248-258, 1997
10. SaleemMA,O'HareMJ, Reiser J, Coward RJ, Inward CD, Farren T, Xing CY, Ni L, Mathieson PW, Mundel P: A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol 13: 630-638, 2002
11. Frenk S, Antonowicz I, Craig JM, Metcoff J: Experimental nephrotic syndrome induced in rats by aminonucleoside; renal lesions and body electrolyte composition. Proc Soc Exp Biol Med 89: 424-427, 1955
12. Caulfield JP, Reid JJ, Farquhar MG: Alterations of the glomerular epithelium in acute aminonucleoside nephrosis. Evidence for formation of occluding junctions and epithelial cell detachment. Lab Invest 34: 43 59, 1976
13. Whiteside CI, Cameron R, Munk S, Levy J: Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. Am J Pathol 142: 1641-1653, 1993
14. Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ: Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009
15. Fishman JA, Karnovsky MJ: Effects of the aminonucleoside of puromycin on glomerular epithelial cells in vitro. Am J Pathol 118: 398-407, 1985
16. Marshall CB, Pippin JW, Krofft RD, Shankland SJ: Puromycin aminonucleoside induces oxidant-dependent DNA damage in podocytes in vitro and in vivo. Kidney Int 70: 1962-1973, 2006
17. Kawasaki Y: Mizoribine: A new approach in the treatment of renal disease. Clin Dev Immunol 2009: 681482, 2009
18. Takeuchi S, Hiromura K, Tomioka M, Takahashi S, Sakairi T, Maeshima A, Kaneko Y, Kuroiwa T, Nojima Y: The immunosuppressive drugmizoribine directly prevents podocyte injury in puromycin aminonucleoside nephrosis. Nephron, Exp Nephrol 116: e3-e10, 2010
19. Wada T, Pippin JW, Marshall CB, Griffin SV, Shankland SJ: Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: Role of p53 and Bcl-2-related family proteins. J Am Soc Nephrol 16: 2615-2625, 2005
20. Ransom RF, Lam NG, Hallett MA, Atkinson SJ, Smoyer WE: Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int 68: 2473-2483, 2005
21. Yamauchi K, Takano Y, Kasai A, Hayakawa K, Hiramatsu N, Enomoto N, Yao J, Kitamura M: Screening and identification of substances that regulate nephrin gene expression using engineered reporter podocytes. Kidney Int 70: 892-900, 2006
22. Xing CY, Saleem MA, Coward RJ, Ni L, Witherden IR, Mathieson PW: Direct effects of dexamethasone on human podocytes. Kidney Int 70: 1038-1045, 2006
23. Zhang JH, Chung TD, Oldenburg KR: A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4: 67-73, 1999
24. Wang L, Ellis MJ, Fields TA, Howell DN, Spurney RF: Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis. Kidney Blood Press Res 31: 111-121, 2008
25. Koshikawa M, Mukoyama M, Mori K, Suganami T, Sawai K, Yoshioka T, Nagae T, Yokoi H, Kawachi H, Shimizu F, Sugawara A, Nakao K: Role of p38mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome.JAmSocNephrol 16: 2690-2701, 2005
26. Pengal R, Guess AJ, Agrawal S, Manley J, Ransom RF, Mourey RJ, Benndorf R, Smoyer WE: Inhibition of the protein kinase MK-2 protects podocytes fromnephrotic syndrome-related injury. AmJ Physiol Renal Physiol 301: F509-F519, 2011
27. Pozzi A, Zent R: Integrins in kidney disease. J Am Soc Nephrol 24: 1034-1039, 2013
28. Pozzi A, Jarad G, Moeckel GW, Coffa S, Zhang X, Gewin L, Eremina V, Hudson BG, Borza DB, Harris RC, Holzman LB, Phillips CL, Fassler R, Quaggin SE,Miner JH, Zent R: Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol 316: 288-301, 2008
29. Kanasaki K, Kanda Y, Palmsten K, Tanjore H, Lee SB, Lebleu VS, Gattone VH Jr., Kalluri R: Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus. Dev Biol 313: 584-593, 2008
30. Yu CC, Fornoni A,Weins A, Hakroush S, Maiguel D, Sageshima J, Chen L,Ciancio G, FaridiMH, BehrD,Campbell KN,Chang JM,ChenHC,Oh J, Faul C, Arnaout MA, Fiorina P, Gupta V, Greka A, Burke GW 3rd, Mundel P: Abatacept in B7-1-positive proteinuric kidney disease. N Engl JMed 369: 2416-2423, 2013
31. Tian X, Kim JJ, Monkley SM, Gotoh N, Nandez R, Soda K, Inoue K, Balkin DM, Hassan H, Son SH, Lee Y, Moeckel G, Calderwood DA, Holzman LB, CritchleyDR, Zent R, Reiser J, Ishibe S: Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance. J Clin Invest 124: 1098-1113, 2014
32. Krishnamurti U, Zhou B, FanWW, Tsilibary E,Wayner E, Kim Y, Kashtan CE, Michael A: Puromycin aminonucleoside suppresses integrin expression in cultured glomerular epithelial cells. J Am Soc Nephrol 12: 758-766, 2001
33. Potla U, Ni J, Vadaparampil J, Yang G, Leventhal JS, Campbell KN, Chuang PY, Morozov A, He JC, D'Agati VD, Klotman PE, Kaufman L: Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis-associated glomerular injury. J Clin Invest 124: 1757-1769, 2014
34. Xu Y, Zhu X, Hahm HS,WeiW, Hao E, Hayek A, Ding S: Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules. Proc Natl Acad Sci U S A 107: 8129 8134, 2010
35. Lenter M, Uhlig H, Hamann A, Jenö P, Imhof B, Vestweber D: A monoclonal antibody against an activation epitope on mouse integrin chain beta 1 blocks adhesion of lymphocytes to the endothelial integrin alpha 6 beta 1. Proc Natl Acad Sci U S A 90: 9051 9055, 1993
36. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, SugimotoH, Kalluri R, SharpeAH, Kreidberg JA,Mundel P: Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113: 1390-1397, 2004
37. Alachkar N, Carter-Monroe N, Reiser J: Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med 370: 1263-1264, 2014
38. Wei C, Möller CC, Altintas MM, Li J, Schwarz K, Zacchigna S, Xie L, Henger A, Schmid H, Rastaldi MP, Cowan P, Kretzler M, Parrilla R, Bendayan M, Gupta V, Nikolic B, Kalluri R, Carmeliet P, Mundel P, Reiser J: Modification of kidney barrier function by the urokinase receptor. Nat Med 14: 55-63, 2008
39. Mundel P, Heid HW, Mundel TM, Krüger M, Reiser J, Kriz W: Synaptopodin: An actin-associated protein in telencephalic dendrites and renal podocytes. J Cell Biol 139: 193-204, 1997
40. Swinney DC, Anthony J: Howwere newmedicines discovered? Nat Rev Drug Discov 10: 507-519, 2011
41. Lee JA, Berg EL: Neoclassic drug discovery: The case for lead generation using phenotypic and functional approaches. J Biomol Screen 18: 1143-1155, 2013
42. Hidaka T, Suzuki Y, Yamashita M, Shibata T, Tanaka Y, Horikoshi S, Tomino Y: Amelioration of crescentic glomerulonephritis by RhoA kinase inhibitor, Fasudil, through podocyte protection and prevention of leukocyte migration. Am J Pathol 172: 603-614, 2008
43. Kanda T, Wakino S, Hayashi K, Homma K, Ozawa Y, Saruta T: Effect of fasudil on Rho-kinase and nephropathy in subtotally nephrectomized spontaneously hypertensive rats. Kidney Int 64: 2009-2019, 2003
44. Nishikimi T, Matsuoka H: Molecular mechanisms and therapeutic strategies of chronic renal injury: Renoprotective effect of rho-kinase inhibitor in hypertensive glomerulosclerosis. J Pharmacol Sci 100: 22 28, 2006
45. Sakurai N, Kuroiwa T, Ikeuchi H, Hiramatsu N, Takeuchi S, Tomioka M, Shigehara T, Maeshima A, Kaneko Y, Hiromura K, Kopp JB, Nojima Y: Fluvastatin prevents podocyte injury in a murine model of HIV-associated nephropathy. Nephrol Dial Transplant 24: 2378-2383, 2009
46. Shibata S, Nagase M, Fujita T: Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling. J AmSoc Nephrol 17: 754-764, 2006
47. Quintavalle M, Elia L, Price JH, Heynen-Genel S, Courtneidge SA: A cell-based high-content screening assay reveals activators and inhibitors of cancer cell invasion. Sci Signal 4: ra49, 2011
48. Singh S, Carpenter AE, Genovesio A: Increasing the content of highcontent screening: An overview. J Biomol Screen 19: 640-650, 2014
49. Sachs N, Claessen N, Aten J, Kreft M, Teske GJ, Koeman A, Zuurbier CJ, Janssen H, Sonnenberg A: Blood pressure influences end-stage renal disease ofCd151 knockoutmice.JClin Invest 122: 348-358, 2012
50. Maiguel D, FaridiMH,Wei C, Kuwano Y, Balla KM, Hernandez D, Barth CJ, Lugo G, DonnellyM, Nayer A, Moita LF, Schürer S, Traver D, Ruiz P, Vazquez-Padron RI, Ley K, Reiser J, Gupta V: Small molecule-mediated activation of the integrin CD11b/CD18 reduces inflammatory disease. Sci Signal 4: ra57, 2011
51. Atkinson SJ, Hosford MA, Molitoris BA: Mechanism of actin polymerization in cellular ATP depletion. J Biol Chem279: 5194-5199, 2004
52. Catanuto P, Doublier S, Lupia E, Fornoni A, Berho M, KarlM, StrikerGE, Xia X, Elliot S: 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes. Kidney Int 75: 1194-1201, 2009
53. Doublier S, Lupia E, Catanuto P, Periera-Simon S, Xia X, Korach K, Berho M, Elliot SJ, KarlM: Testosterone and 17b-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney Int 79: 404-413, 2011
54. Catanuto P, Fornoni A, Pereira-Simon S, Wu F, Burnstein KL, Xia X, Conti F, Lenzi A, Elliot S: In vivo 17b-estradiol treatment contributes to podocyte actin stabilization in female db/db mice. Endocrinology 153: 5888-5895, 2012