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Alteration of histone H3K4 methylation in glomerular podocytes associated with proteinuria in patients with membranous nephropathy.
https://asahikawa-med.repo.nii.ac.jp/records/5699
https://asahikawa-med.repo.nii.ac.jp/records/5699321a057f-dc2a-4257-889c-3914d7d6b490
| 名前 / ファイル | ライセンス | アクション |
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6759.pdf (3.7 MB)
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| Item type | 学術雑誌論文 / Journal Article_02(1) | |||||||||||||
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| 公開日 | 2017-07-21 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Alteration of histone H3K4 methylation in glomerular podocytes associated with proteinuria in patients with membranous nephropathy. | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 資源タイプ | ||||||||||||||
| 資源タイプ | journal article | |||||||||||||
| 著者 |
藤野, 貴行
× 藤野, 貴行
× 長谷部, 直幸
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| 著者 ローマ字 | ||||||||||||||
| Fujino, Takayuki | ||||||||||||||
| 著者 ローマ字 | ||||||||||||||
| Hasebe, Naoyuki | ||||||||||||||
| 書誌情報 |
BMC Nephrology 巻 17, p. 179, 発行日 2016-11-01 |
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| ISSN | ||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||
| 収録物識別子 | 1471-2369 | |||||||||||||
| DOI | ||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | 10.1186/s12882-016-0390-8 | |||||||||||||
| 識別番号 その他 | ||||||||||||||
| 内容記述タイプ | Other | |||||||||||||
| 内容記述 | PMID：27855638 | |||||||||||||
| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | BACKGROUND: \nHistone H3K4 trimethylation (H3K4 me3) is found in active euchromatic regions and plays an important role in podocyte function in which actin filaments are abundant in the foot processes. The pathogenesis of membranous nephropathy (MN), the most prevalent cause of primary nephrotic syndrome in the middle-aged and elderly, is podocyte dysfunction. METHODS: \nWe investigated the role of H3K4 me3 in podocyte dysfunction in nephrotic syndrome using cultured podocytes and a mouse proteinuria model induced by LPS. We examined renal biopsy specimens from six patients with nephrotic syndrome caused by Phospholipase-A2-Receptor-positive primary MN. RESULTS: \nH3K4 me3 exhibited a pattern of nuclear expression in podocytes of the kidneys from patients with MN. The overlapping expression of H3K4 me3 and cathepsin L (a potent endoprotease causing the breakdown of actin-associated protein within lysosomal compartments in kidney podocytes) were higher in patients with MN compared with the controls. Histone H3K4 me3 in kidney podocytes was negatively correlated with synaptopodin, an actin-associated protein in podocytes, and the expression was positively correlated with the proteinuria levels in patients with MN. Histone H3K4 me3 levels were elevated in podocytes of LPS-treated mice, combined with an increase in podocyte swelling, an elevation of serum creatinine and urine albumin, increased cathepsin L, and decreased synaptopodin expression. Histone H3K4 me3 levels at the cathepsin L promoter were elevated in LPS-exposed mouse kidneys. The administration of shRNA against MLL3 (an H3K4 methyltransferase) to LPS-treated mice and cultured podocytes co-cultured with LPS-stimulated macrophages ameliorated podocyte swelling, an elevation in the serum creatinine and urine albumin levels and an increased expression of histone H3K4 me3 and cathepsin L, and a decreased expression of synaptopodin and increase in histone H3K4 me3 levels at the cathepsin L promoter. CONCLUSIONS: \nHistone H3K4 me3 upregulation may be involved in podocyte dysfunction and the pathophysiology of MN. Targeting this epigenetic signature of histone H3K4 me3 followed by modulating the actin dynamics may be an effective strategy to ameliorate the consequences of MN. |
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| 注記 | ||||||||||||||
| 内容記述タイプ | Other | |||||||||||||
| 注記 | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) | |||||||||||||
| 資源タイプ | ||||||||||||||
| 内容記述タイプ | Other | |||||||||||||
| 資源タイプ | text | |||||||||||||
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| 出版タイプ | VoR | |||||||||||||
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| 内容記述タイプ | Other | |||||||||||||
| 内容記述 | application/pdf | |||||||||||||
| ID(XooNIps) | ||||||||||||||
| 27855638 | ||||||||||||||
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| ダウンロード数(XooNIps) | ||||||||||||||
| 1057 | ||||||||||||||
