Role of autophagy in kidney aging and metabolic acidosis
| Project/Area Number |
24591196
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISAKA Yoshitaka 大阪大学, 大学院医学系研究科, 准教授 (00379166)
北村 温美 大阪大学, 医学部附属病院, 助教 (60570356)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | オートファジー / 近位尿細管 / 老化 / アシドーシス / ミトコンドリア / 慢性腎臓病 / ミトファジー / 酸化ストレス / アンモニア / p62 |
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| Outline of Final Research Achievements |
Autophagy plays an essential role for cellular homeostasis. We have previously demonstrated that autophagy protects against ischemia-reperfusion or nephrotoxic injury. Here we tested whether autophagy is involved in kidney aging. Age-dependent high basal autophagy plays a crucial role in counteracting kidney aging through mitochondrial quality control but that lack of up-regulation of autophagic flux in response to metabolic stress with age is associated with age-related kidney diseases. Furthermore, we tested whether autophagy is involved in cellular adaptations of the proximal tubular cell against chronic metabolic acidosis through mitochondrial homeostasis. Metabolic acidosis induces autophagy in the proximal tubular cell, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. These two results provide a new therapeutic option for age-related kidney disease and acidosis by modulating autophagy.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Autophagy protects kidney proximal tubule epithelial cells from mitochondrial metabolic stress2013
Author(s)
Kimura, T., Takahashi, A., Takabatake, Y., Namba, T, Yamamoto, T., Kaimori, J.Y., Matsui, I., Kitamura, H., Niimura, F., Matsusaka T., Soga, T., Rakugi, H., Isaka, Y.
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Journal Title
Autophagy
Volume: 9
Issue: 11
Pages: 1876-1886
DOI
Related Report
Peer Reviewed
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