Establichment of control method for M2-type activated macrophage-mediated progression of childhood CKD.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Fujita Health University
• Principal Investigator: Ikezumi Yohei 藤田医科大学, 医学部, 准教授 (70361897)
• Co-Investigator(Kenkyū-buntansha): 長尾 静子 藤田医科大学, 病態モデル先端医学研究センター, 教授 (20183527) ; 熊谷 直憲 藤田医科大学, 医学部, 講師 (40400329) ; 山田 剛史 新潟大学, 医歯学総合病院, 助教 (90601922)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 慢性糸球体腎炎 / 慢性腎臓病 / 活性化マクロファージ / M2型活性化マクロファージ / 線維化

Outline of Final Research Achievements

In this study, we identified M2-type activated macrophages (M2) involved in the pathogenesis of chronic lesions such as glomerulosclerosis and interstitial fibrosis, which are universally recognized as end-stage pathological findings in all chronic kidney diseases (CKD), and investigated their detailed functional analysis and establishment of a methodology for their regulation.
We found that this macrophage phenotype is activated by steroids, which are commonly used in the treatment of CKD, and contributes to the resolution of nephritis by expressing anti-inflammatory factors, while at the same time being involved in the development of chronic lesions by expressing profibrotic factors. We found that some immunosuppressive drugs such as mizoribine, which is used in combination with steroids as a multidrug therapy, have the ability to reduce the lifespan of M2 and attenuate the progression of chronic lesions.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

わが国の慢性腎臓病(CKD)による透析患者数は増加の一途をたどっており間もなく35万人に達する。本研究は全てのCKDの進展過程で認める腎線維化に関わるマクロファージ(MQ)群の同定とその機序の解明および制御法の確立を目的としたものである。今回の研究により腎組織の線維化に関わるMQ群としてCD163陽性M2型活性化MQ群を同定したこと、およびその制御を可能とする治療薬の一つを見出しこと、またCKDの重要な要因となる慢性糸球体腎炎の治療薬として汎用されるステロイド薬のMQを介した組織線維化への関与を明らかにしたことは、CKDの増加に歯止めをかける上で重要かつ意義ある発見といえる。