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Podocyte hypertrophic stress and detachment precedes hyperglycemia or albuminuria in a rat model of obesity and type2 diabetes-associated nephropathy
http://hdl.handle.net/10458/0002000118
http://hdl.handle.net/10458/0002000118b9acc9ae-f94a-43e1-85c1-68fcedd33aae
| 名前 / ファイル | ライセンス | アクション |
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本文 (3.8 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2023-10-25 | |||||
| タイトル | ||||||
| タイトル | Podocyte hypertrophic stress and detachment precedes hyperglycemia or albuminuria in a rat model of obesity and type2 diabetes-associated nephropathy | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Diabetic nephropathy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Prognostic markers | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
皆川, 明大
× 皆川, 明大× 福田, 顕弘× 佐藤, 祐二× 菊池, 正雄× 北村, 和雄× Wiggins, Roger C.× 藤元, 昭一 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Type2 diabetes-associated nephropathy is the commonest cause of renal failure. Mechanisms responsible are controversial. Leptin-deficient hyperphagic Zucker (fa/fa) rats were modeled to test the hypothesis that glomerular enlargement drives podocyte hypertrophic stress leading to accelerated podocyte detachment, podocyte depletion, albuminuria and progression. By 6weeks, prior to development of either hyperglycemia or albuminuria, fa/fa rats were hyperinsulinemic with high urinary IGF1/2 excretion, gaining weight rapidly, and had 1.6-fold greater glomerular volume than controls (P < 0.01). At this time the podocyte number per glomerulus was not yet reduced although podocytes were already hypertrophically stressed as shown by high podocyte phosphor-ribosomal S6 (a marker of mTORC1 activation), high urinary pellet podocin:nephrin mRNA ratio and accelerated podocyte detachment (high urinary pellet podocin:aquaporin2 mRNA ratio). Subsequently, fa/fa rats became both hyperglycemic and albuminuric. 24 hr urine albumin excretion correlated highly with decreasing podocyte density (R2 = 0.86), as a consequence of both increasing glomerular volume (R2 = 0.70) and decreasing podocyte number (R2 = 0.63). Glomerular podocyte loss rate was quantitatively related to podocyte detachment rate measured by urine pellet mRNAs. Glomerulosclerosis occurred when podocyte density reached <50/106um3. Reducing food intake by 40% to slow growth reduced podocyte hypertrophic stress and “froze” all elements of the progression process in place, but had small effect on hyperglycemia. Glomerular enlargement caused by high growth factor milieu starting in pre-diabetic kidneys appears to be a primary driver of albuminuria in fa/fa rats and thereby an under-recognized target for progression prevention. Progression risk could be identified prior to onset of hyperglycemia or albuminuria, and monitored non-invasively by urinary pellet podocyte mRNA markers. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: Minakawa, A., Fukuda, A., Sato, Y. et al. Podocyte hypertrophic stress and detachment precedes hyperglycemia or albuminuria in a rat model of obesity and type2 diabetes-associated nephropathy. Sci Rep 9, 18485 (2019). https://doi.org/10.1038/s41598-019-54692-z |
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| 言語 | en | |||||
| 書誌情報 |
en : Scientific Reports 巻 9, 号 1, p. 18485 (2019), 発行日 2019-12-06 |
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| 出版者 | ||||||
| 出版者 | Springer Nature | |||||
| 言語 | en | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1038/s41598-019-54692-z | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
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皆川, 明大, 福田, 顕弘, 佐藤, 祐二, 菊池, 正雄, 北村, 和雄, Wiggins, Roger C., 藤元, 昭一, 2019, Podocyte hypertrophic stress and detachment precedes hyperglycemia or albuminuria in a rat model of obesity and type2 diabetes-associated nephropathy: Springer Nature, 18485 (2019)– p.
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