2021 Fiscal Year Final Research Report
Role of protein cross-linking modifications in regulating epithelial mesenchymal transition in renal tubule
Project/Area Number |
19K08675
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Nagoya University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | トランスグルタミナーゼ / タンパク質架橋酵素 / 腎線維化 / 尿細管上皮細胞 / 上皮間葉転換 / 細胞死 |
Outline of Final Research Achievements |
Renal fibrosis is a disease characterized by excessive accumulation of extracellular matrix and loss of renal function associated with tissue stiffening. In the initial pathogenesis of this disease, the induction of transformation from epithelial cells to extracellular matrix-producing fibroblasts (epithelial-mesenchymal transition; EMT) following cellular damage of tubular epithelial cells is considered to be the starting point of the pathogenesis of this disease. Here, we focused on the protein cross-linking enzyme transglutaminase (TG1), which has been studied to play an important role in skin epidermal formation, and found that this enzyme is significantly activated in tubular epithelial cells and exerts a protective effects against EMT. Furthermore, we generated TG1-deficient mice in the renal tubules and examined the effect of this enzyme in a renal injury model, suggesting that TG1 acts to alleviate the pathogenesis of renal disease.
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Free Research Field |
分子病態学
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Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病は成人の8人に1人が罹患する国民病であり、このような腎疾患で共通する病態的特徴である線維化は腎機能予後と強く相関する。尿細管上皮の制御破綻は腎疾患の発症起点として示唆されるものの、これを標的とした有効な制御法は未確立であり、新たな治療法開発のための分子機構の理解が重要である。申請者は先行的研究として腎疾患時に尿細管上皮細胞で活性化するタンパク質架橋酵素TG1に焦点を当て、TG1が尿細管上皮細胞の形質変化における保護的作用に関わることを見出した。本研究は腎疾患の新規予防・治療法の開発のみならず、他臓器が関連する慢性疾患の制御法開発などの波及効果に繋がることが期待される。
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