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雑誌文献

臨床検査50巻5号

2006年05月発行

文献概要

今月の主題 腎疾患と臨床検査 話題

腎臓線維化と低酸素-HIF

著者: 孫大輔1 南学正臣

所属機関: 1東京大学医学部附属病院・腎臓内分泌内科

ページ範囲:P.571 - P.574

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1.はじめに

 慢性腎不全患者が末期腎不全に至る原因として,従来,糸球体高血圧や蛋白尿などが重視されてきたが,近年「低酸素」という病態が注目されてきている.糖尿病性腎症や高血圧性腎硬化症など,腎不全の原因が異なっていても,ある閾値を超えると腎不全は不可逆的に進行していくが,その共通の病態は「final common pathway」と呼ばれ,低酸素がその中心をなすと考えられている.ここでは,低酸素が腎不全の進行にどのように影響を及ぼすのかを,腎線維化との関係を中心に解説する.

参考文献

1) Nangaku M:Hypoxia and tubulointerstitial injury;a final common pathway to end-stage renal failure. Nephron Exp Nephrol 98:e8-12, 2004
2) Nangaku M:Mechanisms of tubulointerstitial injury in the kidney:final common pathways to end-stage renal failure. Intern Med 43:9-17, 2004
3) Nangaku M:Chronic hypoxia and tubulointerstitial injury;a final common pathway to end-stage renal failure. J Am Soc Nephrol 17:17-25, 2006
4) Manotham K, Tanaka T, Matsumoto M, et al:Transdifferentiation of cultured tubular cells induced by hypoxia. Kidney Int 65:871-880, 2004
5) Liu Y:Epithelial to mesenchymal transition in renal fibrogenesis;pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 15:1-12, 2004
6) Norman JT, Clark IM, Garcia PL:Hypoxia promotes fibrogenesis in human renal fibroblasts. Kidney Int 58:2351-2366, 2000
7) Tanaka T, Hanafusa N, Ingelfinger JR, et al:Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF1-mediated upregulation of Bax. Biochem Biophys Res Commun 309:222-231, 2003
8) Tanaka T, Miyata T, Inagi R, et al:Hypoxia-induced apoptosis in cultured glomerular endothelial cells;involvement of mitochondrial pathways. Kidney Int 64:2020-2032, 2003
9) Matsumoto M, Tanaka T, Yamamoto T, et al:Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis. J Am Soc Nephrol 15:1574-1581, 2004
10) Manotham K, Tanaka T, Matsumoto M, et al:Evidence of tubular hypoxia in the early phase in the remnant kidney model. J Am Soc Nephrol 15:1277-1288, 2004
11) Rosenberger C, Mandriota S, Jurgensen JS, et al:Expression of hypoxia-inducible factor-1alpha and-2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol 13:1721-1732, 2002
12) Tanaka T, Miyata T, Inagi R, et al:Hypoxia in renal disease with proteinuria and/or glomerular hypertension. Am J Pathol 165:1979-1992, 2004
13) Manotham K, Tanaka T, Ohse T, et al:A biologic role of HIF-1 in the renal medulla. Kidney Int 67:1428-1439, 2005
14) Matsumoto M, Makino Y, Tanaka T, et al:Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats. J Am Soc Nephrol 14:1825-1832, 2003
15) Tanaka T, Kojima I, Ohse T, et al:Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model. Lab Invest 85:1292-1307, 2005
16) Tanaka T, Kojima I, Ohse T, et al:Hypoxia-inducible factor modulates tubular cell survival in cisplatin nephrotoxicity. Am J Physiol Renal Physiol 289:F1123-1133, 2005
17) Tanaka T, Matsumoto M, Inagi R, et al:Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis. Kidney Int 68:2714-2725, 2005

掲載誌情報

出版社:株式会社医学書院

電子版ISSN:1882-1367

印刷版ISSN:0485-1420

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