Role of mesangial RNA recognition receptors in innate immunity and chronic renal diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461204
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Hirosaki University
• Principal Investigator: Imaizumi Tadaatsu 弘前大学, 医学(系)研究科(研究院), 教授 (90232602)
• Co-Investigator(Kenkyū-buntansha): TANAKA Hiroshi 弘前大学, 教育学部, 教授 (50271820) ; SHIMADA Michiko 弘前大学, 医学部附属病院, 講師 (40463765)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ISG / IFN / RIG-I / TLR3 / CCL5

Outline of Final Research Achievements

Innate immune reactions are important in not only in host defense but also inflammatory renal diseases. Recognition of exogenous or endogenously released RNA by Toll-like receptor 3 (TLR3) induces the expression of interferon (IFN)-beta and activates innate immune reaction and downstream inflammatory reactions in mesangial cells. IFN-beta induces hundreds of IFN-sinducible genes (ISGs). We examined the role of several ISGs in TLR3 / IFN-beta / phosphorylated STAT1 / retinoic acid-inducible gene-I (RIG-I) / CCL5 axis in cultured human mesangial cells, and found that ISG56, ISG54 and ISG60 positively regulates this axis, while ISG15 negatively regulates this axis. These results suggest that TLR3-mediated innate immune reactions are tightly regulated by various ISGs and dysregulation of these ISGs may cause the onset and/or worsening of chronic renal diseases.

Free Research Field

病態生理学