Tubulointerstitial lesion formation in chronic kidney disease mediated by renal adhesion molecule CADM1
| Project/Area Number |
20K07434
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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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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kindai University |
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Principal Investigator |
Hagiyama Man 近畿大学, 医学部, 講師 (60632718)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 上皮変性・アポトーシス / 慢性腎臓病 / 接着分子 / 細胞外切断 / 尿細管間質病変 / 上皮変性 / 細胞外断片 / ELISA / 酵素的切断 |
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| Outline of Research at the Start |
慢性腎臓病では尿細管上皮変性・炎症細胞浸潤・間質線維化より成る尿細管間質病変が生じ、その重篤化が不可逆的な腎機能障害を導くと認識されているが、本病態の分子機序解明は十分ではない。慢性腎臓病では尿細管上皮のIgCAM型接着分子CADM1（cell adhesion molecule 1）の細胞外切断が亢進し、上皮アポトーシスを誘導する。本研究では、皮質間質中に放出された切断産物が、マスト細胞や細胞障害性Tリンパ球を活性化し、炎症・線維化を惹起する責任因子となると考え、CADM1の細胞外切断が慢性腎臓病における尿細管間質病変形成に関与することを明らかにする。
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| Outline of Final Research Achievements |
In chronic kidney disease (CKD), tubulointerstitial damage correlates with progressive decline in renal function, but it is difficult to monitor the severity without renal biopsy. Tumor suppressor CADM1/TSLC1, an IgCAM-type adhesion molecule, is expressed on renal tubular cells, and its increased ectodomain shedding is suggested to contribute to tubular degeneration. A sandwich ELISA for urinary CADM1 was developed using two anti-ectodomain antibodies. Urinary CADM1 concentrations in patients with CKD were measured. Renal biopsy specimens of all patients were pathologically scored for tubulointerstitial lesions using epithelial degeneration, interstitial inflammation, and fibrosis. There was a weak inverse correlation between pathological scores and elevated GFR (eGFR). Notably, this correlation gradually increased in patients with increasing CADM1 concentrations. CADM1 appeared to be a useful marker indicating tubulointerstitial damage from eGFR levels in CKD.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病では尿細管間質病変の重篤度が残腎機能を規定する。近年、新規尿中バイオマーカーが確立されているが、尿細管間質障害の全体を反映しているとは言い難く、腎生検以外にその重篤度を知るのは難しい。国内で1300万人を超える慢性腎臓病患者の治療においては尿細管間質の慢性炎症とそれに続く線維化を制御する必要性が重要視されているが、国内外の多くの研究にもかかわらず、病態の分子機序、特に慢性炎症の引き金となる上位分子は確定していない。本研究は接着分子結合を介した特異性の高い慢性炎症誘導モデルを提唱しており、極めて独創的かつ重要な課題と認識される。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Possible Therapeutic Utility of anti-Cell Adhesion Molecule 1 Antibodies for Malignant Pleural Mesothelioma.2022
Author(s)
Hagiyama M, Mimae T, Wada A, Takeuchi F, Yoneshige A, Inoue T, Kotoku N, Hamada H, Sekido Y, Okada M, Ito A
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Journal Title
Front Cell Dev Biol
Volume: 10
Pages: 945007-945007
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of cell adhesion molecule 1 in human and murine endometrial glandular cells and its increase during the proliferative phase by estrogen and cell density.2021
Author(s)
Kimura R, Otani T, Shiraishi N, Hagiyama M, Yoneshige A, Wada A, Kajiyama H, Takeuchi F, Mizuguchi N, Morishita K, Ito A
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Journal Title
Life Sci
Volume: 283
Pages: 119854-119854
DOI
Related Report
Peer Reviewed / Open Access
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