Glomerular inflammation induced by innate immune reaction in residual glomerular cells and future therapeutic strategy for CKD

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hirosaki University
• Principal Investigator: Tanaka Hiroshi 弘前大学, 教育学部, 教授 (50271820)
• Co-Investigator(Kenkyū-buntansha): 吉田 秀見 弘前大学, 医学研究科, 講師 (40201008) ; 今泉 忠淳 弘前大学, 医学研究科, 教授 (90232602)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 培養ヒトメサンギウム細胞 / 培養ヒト糸球体上皮細胞 / Toll様受容体3 / 慢性腎臓病 / 糸球体腎炎

Outline of Final Research Achievements

We examined the Toll-like receptor (TLR) 3 signaling cascades triggered by polyinosinic-polycytidylic acid, a synthetic analogue of viral dsRNA, that elicites “pseudoviral” infection in cultured human mesangial cells (MCs) and glomerular endothelial cells (GECs), and found that TLR3/IFN-β activation and subsequent regional expressions of proinflammatory chemokines/cytokines in MCs and GECs may be a key trigger in the glomerular inflammatory cascades.
Although glomerular inflammation via innate immunity reportedly plays a pivotal role in the pathogenesis and progression of chronic kidney diseases (CKD), detailed signaling pathways via TLR3 activation in the residual glomerular cells have not always been studied so far.
Considering that TLR3 signaling is implicated in CKD pathogenesis, intervention in these signaling pathways may be a considerable therapeutic strategy for treating CKD in the future.

Free Research Field

小児腎臓病学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病 (CKD)の病態形成には，感染症や内因性リガンドが惹起する自然免疫系 の活性化とこれに伴う慢性炎症の関与が知られているが，その分子病態学的詳細は不明の点が多い。ウイルス感染はCKDの発症機転や増悪因子となることが臨床観察で知られているが，その分子生物学的詳細に関しても不明な点が多い。
今回，培養ヒトメサンギウム細胞 (MCs)，培養ヒト糸球体内皮細胞 (GECs)でのウイルス dsRNAを認識する Toll様受容体3 (TLR3)を介する炎症経路群の詳細を検討，および腎生検組織での免疫染色から，TLR3を起点とする炎症病態の一部が明らかとなり，新規の治療法開発への足掛かりが得られた。