The role of renal and urethral flora and related peptides in renal fibrosis
Project/Area Number |
21K16160
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Mie University |
Principal Investigator |
Nishihama Kota 三重大学, 医学部附属病院, 助教 (90832527)
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | 腎線維化 / 細菌叢 / corisin / 慢性腎疾患 / TGF-β |
Outline of Research at the Start |
本研究では腎特異的TGFβ-TGマウスにおける腎線維化の進行に腎・尿路の細菌叢およびその産生物質の関与の有無を示すことを目標とする。腎特異的TGFβ-TGマウスにおける腎・尿路の細菌叢の変化を確認することに加え、肺特異的TGFβ-TGマウスの肺線維化に影響を及ぼす特定の細菌由来ペプチドであるcorisinの濃度を血液や尿サンプルを用いて測定し、in vitro実験でcorisinが腎細胞株に与える影響につき検討する。細菌叢由来ペプチドが人体に幅広く直接的な影響を及ぼすことを示唆する結果が得られば、今後の臓器線維化に関するバイオマーカーや創薬開発につながる可能性がある。
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Outline of Final Research Achievements |
In mice treated with the microbiota-derived peptide corisin, urinary albumin excretion was increased in the renal fibrosis model compared to the control group, and pathological examination suggested progressive glomerular and tubulointerstitial fibrosis. These results suggest that corisin promotes renal fibrosis in the mouse model of renal fibrosis. In vitro experiments also showed that corisin and corisin-like peptides induced apoptosis in podocyte and Caki-2 cells, and co-stimulation with TGF-β and corisin enhanced apoptosis induction. These results suggest that corisin is involved in the induction of apoptosis in kidney-derived cells.
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Academic Significance and Societal Importance of the Research Achievements |
全ての腎疾患は末期腎不全に至る過程で腎線維化を伴うため、腎線維化の発生機序の解明と進行抑制は腎疾患の治療法の開発における重要な標的となる。今回の研究成果は常在細菌叢のマネジメントを通じて臓器線維化の進行の予測や進行の抑制を目指す新しい治療戦略につながるものと考える。
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Inhibition of a Microbiota-Derived Peptide Ameliorates Established Acute Lung Injury2023
Author(s)
D'Alessandro Fridman V, D'Alessandro-Gabazza CN, Yasuma T, Toda M, Takeshita A, Tomaru A, Tharavecharak S, Lasisi IO, Hess RY, Nishihama K, Fujimoto H, Kobayashi T, Cann I, Gabazza EC.
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Journal Title
American Journal of Pathology
Volume: 23
Issue: 6
Pages: 740-754
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions.2022
Author(s)
D'Alessandro VF, Takeshita A, Yasuma T, Toda M, D'Alessandro-Gabazza CN, Okano Y, Tharavecharak S, Inoue C, Nishihama K, Fujimoto H, Kobayashi T, Yano Y, Gabazza EC.
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Journal Title
Int J Mol Sci.
Volume: 23
Issue: 22
Pages: 146251-19
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis.2022
Author(s)
D'Alessandro-Gabazza CN, Yasuma T, Kobayashi T, Toda M, Abdel-Hamid AM, Fujimoto H, Hataji O, Nakahara H, Takeshita A, Nishihama K, Okano T, Saiki H, Okano Y, Tomaru A, D'Alessandro VF, Shiraishi M, Mizoguchi A, Ono R, Ohtsuka J, Fukumura M, Nosaka T, et al. & Gabazza EC
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Journal Title
Nat Commun
Volume: 13
Issue: 1
Pages: 1558-1558
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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