Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

Journal of Clinical Investigation

Volumn 125, Issue 1, 2015, Pages 141-156

  Gomez, Ivan G ^a,g   MacKenna, Deidre A ^b   Johnson, Bryce G ^a,g   Kaimal, Vivek ^b   Roach, Allie M ^a,g   Ren, Shuyu ^a,g   Nakagawa, Naoki ^a   Xin, Cuiyan ^a   Newitt, Rick ^a   Pandya, Shweta ^b   Xia, Tai He ^c   Liu, Xueqing ^b   Borza, Dorin Bogdan ^d   Grafals, Monica ^e   Shankland, Stuart J ^a   Himmelfarb, Jonathan ^a   Portilla, Didier ^f   Liu, Shiguang ^c   Chau, B Nelson ^b   Duffield, Jeremy S ^a,g  

^a UNIVERSITY OF WASHINGTON   (United States)

^b REGULUS THERAPEUTICS   (United States)

^c GENZYME CORPORATION   (United States)

^d MEHARRY MEDICAL COLLEGE   (United States)

^e GEORGETOWN UNIVERSITY   (United States)

^f UNIVERSITY OF VIRGINIA   (United States)

^g BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI MICRORNA 21 OLIGONUCLEOTIDE; COLLAGEN TYPE 4; MICRORNA 21; OLIGONUCLEOTIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; REACTIVE OXYGEN METABOLITE; RETINOID X RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; ANTISENSE OLIGONUCLEOTIDE; AUTOANTIGEN; MICRORNA; MIRN21 MICRORNA, MOUSE; TRANSCRIPTOME; TYPE IV COLLAGEN ALPHA3 CHAIN;

ALBUMINURIA; ALPORT SYNDROME; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHRONIC KIDNEY DISEASE; CONTROLLED STUDY; DISEASE COURSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; DRUG SYNTHESIS; GENE SILENCING; GLOMERULOSCLEROSIS; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; KIDNEY FIBROSIS; KIDNEY INTERSTITIUM CELL; KIDNEY PROXIMAL TUBULE; KIDNEY TUBULE CELL; KIDNEY TUBULE DAMAGE; KIDNEY TUBULE FUNCTION; MILD RENAL IMPAIRMENT; MITOCHONDRIAL RESPIRATION; MOLECULARLY TARGETED THERAPY; MOUSE; MULTIPLE DRUG DOSE; MYOFIBROBLAST; NEPHRITIS; NONHUMAN; PODOCYTE; PROTEIN PROTEIN INTERACTION; RENAL PROTECTION; SIGNAL TRANSDUCTION; UPREGULATION; 129 MOUSE; ANIMAL; DEFICIENCY; FIBROSIS; GENETICS; KIDNEY; METABOLISM; NEPHRITIS, HEREDITARY; PATHOLOGY;

ANIMALS; AUTOANTIGENS; COLLAGEN TYPE IV; DISEASE PROGRESSION; FIBROSIS; KIDNEY; METABOLIC NETWORKS AND PATHWAYS; MICE, 129 STRAIN; MICRORNAS; NEPHRITIS, HEREDITARY; OLIGORIBONUCLEOTIDES, ANTISENSE; REACTIVE OXYGEN SPECIES; TRANSCRIPTOME; UP-REGULATION;

EID: 84920459959     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI75852     Document Type: Article

References (53)

1. Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, Iacomini J. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci USA. 2010;107(32):14339-14344.
2. Kato M, Natarajan R. MicroRNA circuits in transforming growth factor-β actions and diabetic nephropathy. Semin Nephrol. 2012;32(3):253-260.
3. Thum T, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980-984.
4. Chau BN, et al. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012;4(121):121ra18.
5. Friedman SL, Sheppard D, Duffield JS, Violette S. Therapy for fibrotic diseases: nearing the starting line. Sci Transl Med. 2013;5(167):167sr1.
6. Denby L, et al. miR-21 and miR-214 are consistently modulated during renal injury in rodent models. Am J Pathol. 2011;179(2):661-672.
7. Zhong X, et al. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia. 2013;56(3):663-674.
8. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43-49.
9. Lee R, Feinbaum R, Ambros V. A short history of a short RNA. Cell. 2004;116(2 suppl):S89-S92.
10. Ghosh AK, Quaggin SE, Vaughan DE. Molecu-lar basis of organ fibrosis: potential therapeutic approaches. Exp Biol Med (Maywood). 2013;238(5):461-481.
11. Gomez IG, Grafals M, Portilla D, Duffield JS. MicroRNAs as potential therapeutic targets in kidney disease. J Formos Med Assoc. 2013;112(5):237-243.
12. Anker MC, Arnemann J, Neumann K, Ahrens P, Schmidt H, König R. Alport syndrome with diffuse leiomyomatosis. Am J Med Genet A. 2003;119A(3):381-385.
13. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. 2003;348(25):2543-2556.
14. Heidet L, Gubler M-C. The renal lesions of Alport syndrome. J Am Soc Nephrol. 2009;20(6):1210-1215.
15. Temme J, et al. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. Clin J Am Soc Nephrol. 2012;7(12):1969-1976.
16. Kruegel J, Rubel D, Gross O. Alport syndrome - insights from basic and clinical research. Nat Re v Nephrol. 2013;9(3):170-178.
17. Deltas C, Pierides A, Voskarides K. Molecular genetics of familial hematuric diseases. Nephrol Dial Transplant. 2013;28(12):2946-2960.
18. Crooke ST. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, Florida, USA: CRC Press; 2007.
19. Masarjian L, de Peyster A, Levin AA, Monteith DK. Distribution and excretion of a phospho-rothioate oligonucleotide in rats with experimentally induced renal injury. Oligonucleotides. 2004;14(4):299-310.
20. Gross O, et al. Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int. 2003;63(2):438-446.
21. Heilig CW, et al. GLUT1 regulation of the pro-sclerotic mediators of diabetic nephropathy. Am J Nephrol. 2013;38(1):39-49.
22. Alvarez ML, Distefano JK. The role of non-coding RNAs in diabetic nephropathy: potential applications as biomarkers for disease development and progression. Diabetes Res Clin Pract. 2013;99(1):1-11.
23. Zhou T-B, Drummen GPC, Jiang Z-P, Long Y-B, Qin Y-H. Association of peroxisome proliferator-activated receptors/retinoic acid receptors with renal diseases. J Recept Signal Transduct Res. 2013;33(6):349-352.
24. Krick S, et al. Mpv17l protects against mitochon-drial oxidative stress and apoptosis by activation of Omi/HtrA2 protease. Proc Natl Acad Sci USA. 2008;105(37):14106-14111.
25. Yeung CK, Shen DD, Thummel KE, Himmelfarb J. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int. 2014;85(3):522-528.
26. Niwa T, Shimizu H. Indoxyl sulfate induces nephrovascular senescence. J Ren Nutr. 2012;22(1):102-106.
27. Duffield JS. Cellular and molecular mecha-nisms in kidney fibrosis. J Clin Invest. 2014;124(6):2299-2306.
28. Asada N, et al. Dysfunction of fibroblasts of extra-renal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest. 2011;121(10):3981-3990.
29. Humphreys BD, et al. Fate tracing reveals the pericyte and not epithelial origin of myo-fibroblasts in kidney fibrosis. Am J Pathol. 2010;176(1):85-97.
30. Schrimpf C, Duffield JS. Mechanisms of fibro-sis: the role of the pericyte. Curr Opin Nephrol Hypertens. 2011;20(3):297-305.
31. Molteni A, et al. Cytostatic properties of some angiotensin I converting enzyme inhibitors and of angiotensin II type I receptor antagonists. Curr Pharm Des. 2003;9(9):751-761.
32. Ryu M, Mulay SR, Miosge N, Gross O, Anders H-J. Tumour necrosis factor-α drives Alport glo-merulosclerosis in mice by promoting podocyte apoptosis. J Pathol. 2012;226(1):120-131.
33. Ninichuk V, et al. Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-defi-cient mice with Alport disease. J Am Soc Nephrol. 2005;16(4):977-985.
34. Gross O, et al. Safety and efficacy of the ACE-inhibitor Ramipril in Alport Syndrome: The double-blind, randomized, placebo-controlled, multicenter phase III EARLY PRO-TECT Alport trial in pediatric patients. ISRN Pediatr. 2012;2012:436046.
35. Snyder JJ, Foley RN, Collins AJ. Prevalence of CKD in the United States: a sensitivity analysis using the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis. 2009;53(2):218-228.
36. Satou R, Gonzalez-Villalobos RA. JAK-STAT and the renin-angiotensin system: The role of the JAK-STAT pathway in blood pressure and intrarenal renin-angiotensin system regulation. JAKSTAT. 2012;1(4):250-256.
37. Dugan LL, et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest. 2013;123(11):4888-4899.
38. Köttgen A, et al. Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet. 2009;41(6):712-717.
39. Kang JS, et al. Loss of α3/α4(IV) collagen from the glomerular basement membrane induces a strain-dependent isoform switch to α5α6(IV) collagen associated with longer renal survival in Col4a3-/-Alport mice. J Am Soc Nephrol. 2006;17(7):1962-1969.
40. Korstanje R, et al. A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers. Kidney Int. 2014;85(6):1461-1468.
41. Boulanger JH, et al. Identification of the pathological role of miR-21 in Alport's kidney disease [Abstract]. J Am Soc Nephrol. 2013;24:525A.
42. Inoki K, et al. mTORC1 activation in podo-cytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest. 2011;121(6):2181-2196.
43. Li S, et al. Proximal tubule PPARα attenuates renal fibrosis and inflammation caused by unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2013;305(5):F618-F627.
44. Cimini A, Cerù MP. Emerging roles of peroxi-some proliferator-activated receptors (PPARs) in the regulation of neural stem cells proliferation and differentiation. Stem Cell Rev. 2008;4(4):293-303.
45. Boor P, et al. The peroxisome proliferator-activat-ed receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats. Kidney Int. 2011;80(11):1182-1197.
46. Kashihara N, Haruna Y, Kondeti VK, Kanwar YS. Oxidative stress in diabetic nephropathy. Curr Med Chem. 2010;17(34):4256-4269.
47. Mailloux RJ, Harper M-E. Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med. 2011;51(6):1106-1115.
48. Modlinger PS, Wilcox CS, Aslam S. Nitric oxide, oxidative stress, and progression of chronic renal failure. Semin Nephrol. 2004;24(4):354-365.
49. Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014;124(6):2333-2340.
50. Cosgrove D, et al. Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. Genes Dev. 1996;10(23):2981-2992.
51. Levin AA, Yu RZ, Geary RS. Basic principles of the pharmacokinetics of antisense oligonucle-otide drugs. In: Crooke ST, ed. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, Florida, USA: CRC Press; 2007:183-216.
52. Swayze EE, Bhat B. The medicinal chemistry of oligonucleotides. In: Crooke ST, ed. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, Florida, USA: CRC Press; 2007:143-182.
53. Davis S, et al. Potent inhibition of microRNA in vivo without degradation. Nucleic Acids Res. 2009;37(1):70-77.