リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「インターロイキン1受容体関連キナーゼ4(IRAK-4)阻害剤AS2444697の腎疾患モデルにおける薬効評価および奏功機序の解析」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

インターロイキン1受容体関連キナーゼ4(IRAK-4)阻害剤AS2444697の腎疾患モデルにおける薬効評価および奏功機序の解析

近藤, 光量 筑波大学 DOI:10.15068/0002005711

2022.11.28

概要

Renal inflammation is a final common pathway of chronic kidney disease (CKD) including diabetic nephropathy (DN), which is the leading cause of end-stage renal disease and is associated with high cardiovascular risk and significant morbidity and mortality. Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) is a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced activation of proinflammatory mediators. In this study, it has been hypothesized that if inflammation plays a key role in renal failure, then the anti-inflammatory effect of IRAK-4 inhibitor should be effective in improving CKD. The renoprotective properties of IRAK-4 inhibitor AS2444697 in 5/6 nephrectomized (Nx) rats as a model of CKD and in KK/Ay type 2 diabetic mice were investigated. The results showed that repeated administration of AS2444697 significantly reduced urinary protein excretion and prevented the development of glomerulosclerosis and interstitial fibrosis and showed beneficial effects on renal function in 5/6Nx rats. In addition, AS2444697 improved renal injury, tubular injury markers, and glomerular podocyte injury markers in KK/Ay mice. Furthermore, AS2444697 attenuated plasma levels of proinflammatory cytokines in both 5/6Nx rats and KK/Ay mice. These results suggest that AS2444697 attenuates the progression of CKD and DN mainly via anti-inflammatory mechanisms through inhibition of IRAK-4 activity and may therefore represent a promising therapeutic option for patients in CKD including DN.

この論文で使われている画像

参考文献

Akmal M. 2001. Hemodialysis in diabetic patients. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation 38: S195-S199.

Amdur RL, Feldman HI, Gupta J, Yang W, Kanetsky P, Shlipak M, Rahman M, Lash JP, Townsend RR, Ojo A, Roy-Chaudhury A, Go AS, Joffe M, He J, Balakrishnan VS, Kimmel PL, Kusek JW, Raj DS. 2016. Inflammation and progression of CKD: The CRIC study. Clinical Journal of the American Society of Nephrology 11: 1546-1556.

Atkinson MA, Eisenbarth GS. 2001. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet (London, England) 358: 221-229.

Booth G, Stalker TJ, Lefer AM, Scalia R, 2002. Mechanisms of amelioration of glucose-induced endothelial dysfunction following inhibition of protein kinase C in vivo. Diabetes 51: 1556-1564.

Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. 2001. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. The New England Journal of Medicine 345: 861-869.

Carrero JJ, Stenvinkel P. 2009. Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: a hypothesis proposal. Clinical Journal of the American Society of Nephrology 4: S49-55.

Cha JJ, Hyun YY, Lee MH, Kim JE, Nam DH, Song HK, Kang YS, Lee JE, Kim HW, Han JY, Cha DR. 2013. Renal protective effects of toll-like receptor 4 signaling blockade in type 2 diabetic mice. Endocrinology 154: 2144-2155.

Cho ME, Kopp JB. 2010. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opinion on Investigational Drugs 19: 275-283.

Creely SJ, McTernan PG, Kusminski CM, Fisher ff M, Da Silva NF, Khanolkar M, Evans M, Harte AL, Kumar S. 2007. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. American Journal of Physiology-Endocrinology and Metabolism 292: E740-E747.

Donate-Correa J, Martin-Nunez E, Muros-de-Fuentes M, Mora-Fernandez C, Navarro-Gonzalez JF. 2015. Inflammatory cytokines in diabetic nephropathy. Journal of Diabetes Research 2015: Article ID 948417, 9 pages Donath MY, Shoelson SE. 2011. Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology 11: 98-107.

Elmarakby AA, Sullivan JC. 2012. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovascular Therapeutics 30: 49-59.

Fiordaliso F, Cuccovillo I, Bianchi R, Bai A, Doni M, Salio M, De Angelis N, Ghezzi P, Latini R, Masson S. 2006. Cardiovascular oxidative stress is reduced by an ACE inhibitor in a rat model of streptozotocin-induced diabetes. Life Sciences 79: 121-129.

Fioretto P, Dodson PM, Ziegler D, Rosenson RS. 2010. Residual microvascular risk in diabetes: unmet needs and future directions. Nature Reviews Endocrinology 6: 19-25.

Fried L, Solomon C, Shlipak M, Seliger S, Stehman-Breen C, Bleyer AJ, Chaves P, Furberg C, Kuler L, Newman A. 2004. Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. Journal of the American Society of Nephrology 15: 3184-3191.

Ghosh SS, Krieg R, Massey HD, Sica DA, Fakhry I, Ghosh S, Gehr TW. 2012. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in 5/6 nephrectomized rats: role of phospholipase and cyclooxygenase. American Journal of Physiology - Renal Physiology 15: F439- F454.

Giacco F, Brownlee M. 2010. Oxidative stress and diabetic complications. Circulation Research 107: 1058-1070.

Giménez N, Schulz R, Higashi M, Aymerich M, Villamor N, Delgado J, Juan M, López-Guerra M, Campo E, Rosich L, Seiffert M, Colomer D. 2020. Targeting IRAK-4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia. Leukemia 34: 100-114.

Hasegawa G, Nakano K, Sawada M, Uno K, Shibayama Y, Ienaga K, Kondo M. 1991. Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy. Kidney International 40: 1007-1012.

Imanishi J, Ishikawa T, Imamura E, Mizuhara H, Iwaoka H, Evelyn B, Inami H, Mizutani T, Watanabe J, Usuda H, Nagashima S, Ito T, Kontani T, Shimizu Y, Mutoh S. 2011. Anti-inflammatory profile of AS2444697, a novel interleukin-1 receptor-associated kinase-4 inhibitor. Arthritis & Rheumatology 63: S390.

Ishidoya S, Morrissey J, McCracken R, Reyes A, Klahr S. 1995. Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney International 47: 1285-1294.

Kajitani N, Shikata K, Nakamura A, Nakatou T, Hiramatsu M, Makino H. 2010. Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Research and Clinical Practice 88: 171-176.

Kim HJ, Vaziri ND, Norris K, An WS, Quiroz Y, Rodriguez-Iturbe B. 2010. High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clinical and Experimental Nephrology 14: 536– 547.

Kim TW, Staschke K, Bulek K, Yao J, Peters K, Oh KH, Vandenburg Y, Xiao H, Qian W, Hamilton T, Min B, Sen G, Gilmour R, Li X. 2007. A critical role for IRAK-4 kinase activity in Toll-like receptor- mediated innate immunity. Journal of Experimental Medicine 204: 1025-1036.

Kliem V, Johnson RJ, Alpers CE, Yoshimura A, Couser WG, Koch KM, Floege J. 1996. Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats. Kidney International. 49: 666-678.

Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HH, Yang K, Chrabieh M, Issekutz AC, Cunningham CK, Gallin J, Holland SM, Roifman C, Ehl S, Smart J, Tang M, Barrat FJ, Levy O, McDonald D, Day-Good NK, Miller R, Takada H, Hara T, Al-Hajjar S, Al-Ghonaium A, Speert D, Sanlaville D, Li X, Geissmann F, Vivier E, Marodi L, Garty BZ, Chapel H, Rodriguez-Gallego C, Bossuyt X, Abel L, Puel A, Casanova JL. 2007. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. Journal of Experimental Medicine 204: 2407-2422.

Kurata A, Nishizawa H, Kihara S, Maeda N, Sonoda M, Okada T, Ohashi K, Hibuse T, Fujita K, Yasui A, Hiuge A, Kumada M, Kuriyama H, Shimomura I, Funahashi T. 2006. Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney International 70: 1717-1724.

Lambers Heerspink HJ, de Zeeuw D. 2013. Novel drugs and intervention strategies for the treatment of chronic kidney disease. British Journal of Clinical Pharmacology 76: 536-550.

Lebleu VS, Sugimoto H, Miller CA, Gattone VH 2nd, Kalluri R. 2008. Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease. Laboratory Investigation 88: 284-292.

Li S, Strelow A, Fontana EJ, Wesche H. 2002. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proceedings of the National Academy of Sciences of the United States of America 16: 5567-5572.

Lin M, Tang SC. 2014. Toll-like receptors: sensing and reacting to diabetic injury in the kidney. Nephrology Dialysis Transplantation 29: 746-754.

Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS. 2005. The renoprotective potential of pentoxifylline in chronic kidney disease. Journal of the Chinese Medical Association 68: 99-105.

Lopez-Novoa JM, Martinez-Salgado C, Rodriguez-Pena AB, Lopez-Hernandez FJ. 2010. Common pathophysiological mechanisms of chronic kidney disease: therapeutic perspectives. Pharmacology and Therapeutics 128: 61–81.

Matsui H, Suzuki M, Tsukuda R, Iida K, Miyasaka M, Ikeda H, 1996. Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. Diabetes Research and Clinical Practice 32: 1-9.

Medvedev AE, Lentschat A, Kuhns DB, Blanco JC, Salkowski C, Zhang S, Arditi M, Gallin JI, Vogel SN. 2003. Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. Journal of Experimental Medicine 18: 521-531.

Mullard A. 2020. IRAK-4 degrader to take on innate immunity. Nature Biotechnology 38: 1221-1223. Nakamura A, Shikata K, Hiramatsu M, Nakatou T, Kitamura T, Wada J, Itoshima T, Makino H. 2005. Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care 28: 2890-2895.

Nakhaee A, Bokaeian M, Saravani M, Farhangi A, Akbarzadeh A. 2009. Attenuation of oxidative stress in streptozotocin-induced diabetic rats by Eucalyptus globulus. Indian Journal of Clinical Biochemistry 24: 419-425.

Nangaku M. 2006. Chronic hypoxia and tubulointerstitial injury: A final common pathway to end-stage renal failure. Journal of the American Society of Nephrology 17: 17-25.

Navarro-Gonzalez JF, Mora-Fernandez C. 2008. The role of inflammatory cytokines in diabetic nephropathy. Journal of the American Society of Nephrology 19: 433-442.

Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, Himmelfarb J. 2004. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney International 65: 1009-1016.

Ortega LM, Fornoni A. 2010. Role of cytokines in the pathogenesis of acute and chronic kidney disease, glomerulonephritis, and end-stage kidney disease. International Journal of Interferon, Cytokine and Mediator Research 2: 49-62.

Osafune K. 2021. Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems. Artificial Organs 45: 447-453.

Palsson R, Patel UD. 2014. Cardiovascular complications of diabetic kidney disease. Advances in Chronic Kidney Disease 21: 273-280.

Pereira BJ, Shapiro L, King AJ, Falagas ME, Strom JA, Dinarello CA. 1994. Plasma levels of IL-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. Kidney International 45: 890-896.

Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jummah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL. 2003. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299: 2076-2079.

Pozzi C, Andrulli S, Pani A, Scaini P, Roccatello D, Fogazzi G, Pecchini P, Rustichelli R, Finocchiaro P, Del Vecchio L, Locatelli F. 2013. IgA nephropathy with severe chronic renal failure: a randomized controlled trial of corticosteroids and azathioprine. Journal of Nephrology 26: 86-93.

Ravera M, Re M, Deferrari L, Vettoretti S, Deferrari G. 2006. Importance of blood pressure control in chronic kidney disease. Journal of the American Society of Nephrology 17: S98-S103.

Shaw JE, Sicree RA, Zimme, PZ. 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice 87: 4-14.

Shikata K, Makino H. 2013. Microinflammation in the pathogenesis of diabetic nephropathy. Journal of Diabetes Investigation 4: 142-149.

Silverstein DM. 2009. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatric Nephrology 24: 1445-1452.

Suliman ME, Stenvinkel P. 2008. Contribution of inflammation to vascular disease in chronic kidney disease patients. Saudi Journal of Kidney Diseases and Transplantation 19: 329-345.

Suzuki N, Suzuki S, Duncan GS, Millar DG, Wada T, Mirtsos C, Takada H, Wakeham A, Itie A, Li S, Penninger JM, Wesche H, Ohashi PS, Mak TW, Yeh WC. 2002. Severe impairment of interleukin- 1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 18: 750-756.

Taal MW, Zandi-Nejad K, Weening B, Shahsafaei A, Kato S, Lee KW, Ziai F, Jiang T, Brenner BM, MacKenzie HS. 2000. Proinflammatory gene expression and macrophage recruitment in the rat remnant kidney. Kidney International 58: 1664–1676.

Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. 2013. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. European Journal of Pharmacology 715: 246-255. Tahara A, Takasu T. 2018. Prevention of progression of diabetic nephropathy by the SGLT2 inhibitor ipragliflozin in uninephrectomized type 2 diabetic mice. European Journal of Pharmacology 830: 68-75.

Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E. 2017. Characterization and comparison of SGLT2 inhibitors: Part 3. Effects on diabetic complications in type 2 diabetic mice. European Journal of Pharmacology 809: 163-171.

Tavafi M. 2013. Complexity of diabetic nephropathy pathogenesis and design of investigations. Journal of Renal Injury Prevention 2: 59-62.

Uehara Y, Kawabata Y, Shirahase H, Wada K, Hashizume Y, Morishita S, Numabe A, Iwai J, Matsuoka H, Sugimoto T. 1992. Radical scavenging properties of indapamide and renal protection in Dahl salt- sensitive rats. Hypertension Research 15: 17-26.

Umar S, Palasiewicz K, Van Raemdonck K, Volin MV, Romay B, Amin MA, Zomorrodi RK, Arami S, Gonzalez M, Rao V, Zanotti B, David A. Fox DA, Sweiss N, Shahrara, S. 2021. IRAK-4 inhibition: A promising strategy for treating RA joint inflammation and bone erosion. Cellular & Molecular Immunology 18: 2199-2210.

van Dieren S, Beulens JW, van der Schouw YT, Grobbee DE, Neal B. 2010. The global burden of diabetes and its complications: an emerging pandemic. The European Journal of Cardiovascular Prevention and Rehabilitation 17: S3-S8.

Wang Z, Wesche H, Stevens T, Walker N, Yeh WC. 2009. IRAK-4 inhibitors for inflammation. Current Topics in Medicinal Chemistry 9: 724-737.

Wolf G, Ziyadeh FN. 2007. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiology 106: 26-31.

飯野 靖彦. 2007. 一目でわかる腎臓 第 2 版. メディカル・サイエンス・インターナショナル: 2-5.

厚生労働省. 2019.「自覚症状のない糖尿病の重症化を防ぐために。−国民健康保険における糖尿病性腎症重症化予防の取組に関する調査−」: 1-2.

槙野 博史. 1999. 糖尿病性腎症-発症・進展機序と治療. 診断と治療社: 192-196.

日本腎臓学会. 2018. エビデンスに基づくCKD 診療ガイドライン. 東京医学社: 2-3.

日本透析学会. 2021. わが国の慢性透析療法の現況. 透析会誌 54: 611-657.

奥田 俊洋. 2000. わかりやすい腎臓の構造と機能. 中外医学社: 1-13.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る