Elucidation of the molecular basis of proteinuria suppression by the acute phase protein orosomucoid and its application to the treatment of chronic kidney disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19340
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Watanabe Hiroshi 熊本大学, 大学院生命科学研究部(薬), 教授 (70398220)
• Co-Investigator(Kenkyū-buntansha): 丸山 徹 熊本大学, 大学院生命科学研究部(薬), 教授 (90423657)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: オロソムコイド / AGP / 蛋白尿 / 糸球体バリア / 炎症 / AKI to CKD

Outline of Final Research Achievements

Reducing proteinuria is an important issue in preventing the progression of chronic kidney disease (CKD). On the other hand, it has been suggested that chronic inflammation and a decline in the barrier function of glomerular endothelial cells are involved in the appearance of proteinuria. If a drug that effectively controls these two factors can be developed, it is expected to have the potential to become an innovative drug for the treatment of kidney disease. In this study, we used AGP-KO mice to elucidate the pathophysiological role of orosomucoid (α1-acid glycoprotein: AGP) in 1) AKI to CKD, 2) adriamycin nephropathy and 3) sepsis. In addition, the results of exogenous AGP administration to various disease models showed that AGP may be a new therapeutic agent for CKD.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

根本治療の無いCKD患者の増加が懸念される中で、AGPを利用した本腎疾患治療戦略は、CKDの予防と治療に貢献するものと考えられる。また、AGPによる蛋白尿抑制の分子機構解明は、今後のCKD治療薬開発のブレークスルーになると思われ、その学術的意義や社会的意義は高い。また、今回用いたAGPは、献血由来の血漿成分から血液製剤成分を分取した後の廃棄血漿を用いて、自施設で単離・精製したものである。すなわち、AGPの活用は貴重な献血成分を有効活用する観点からも大変意義深いと思われる。