2021 Fiscal Year Final Research Report
Role of interleukin-34 in the development of experimental kidney disease models
| Project/Area Number |
19K08734
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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 53040:Nephrology-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Interleukin-34 / マクロファージ / 抗IL-34抗体 / 尿細管アポトーシス / 腎線維化 |
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| Outline of Final Research Achievements |
Thus far, the influence of interleukin-34 (IL-34), identified as macrophage (Mq) mediator, on renal disorder remained to be fully elucidated. In this study using cisplatin induced nephrotoxicity (CP-N) and unilateral ureteral obstruction (UUO) model mice, significant elevation of IL-34 and its two receptors, cFMS and PTP-z, were determined on damaged tubular epithelial cells (TECs). Moreover, we administrated the anti-IL-34 neutralizing antibody to CP-N or UUO model mice, followed by apparent improvement of TECs apoptosis or renal fibrosis with significant reduction of Mq infiltration in damaged renal tissues. Additionally, in the experiment with cultured mice TECs, treatment with anti-IL-34 Ab significantly inhibited CP or TGF-β induced expressions of apoptosis regulatory molecules, fibrogenetic genes, and ERK phosphorylation.
Take together, IL-34 might be involved in the pathogenesis of renal damage, and IL-34 inhibition with neutralizing antibody might have therapeutic potential.
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| Free Research Field |
腎臓病全般、糸球体腎炎、ネフローゼ、腎と免疫
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、IL-34が尿細管上皮細胞障害や腎の線維化に関与し、それらの増悪因子であることことが示された。更に、IL-34を阻害することで急性腎障害や腎線維化の増悪が抑制されることも示された。尿細管上皮細胞障害は急性腎障害の主たる要因であり、腎線維化はすべての腎疾患の終末像とされている。よって、これら急性期から慢性期に及ぶ腎障害の本質的な病態に対しIL-34の関与やそれが治療標的となることを解明できた点は、今後増加することが予想されている腎臓病患者の病態と治療戦略への理解を深める上で、重要な知見になりえたと考えられ、学術的及び社会的な意義の高い検討であったと考える。
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