Tubulointerstitial lesion formation in chronic kidney disease mediated by renal adhesion molecule CADM1

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kindai University
• Principal Investigator: Hagiyama Man 近畿大学, 医学部, 講師 (60632718)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 上皮変性・アポトーシス / 慢性腎臓病 / 接着分子 / 細胞外切断

Outline of Final Research Achievements

In chronic kidney disease (CKD), tubulointerstitial damage correlates with progressive decline in renal function, but it is difficult to monitor the severity without renal biopsy. Tumor suppressor CADM1/TSLC1, an IgCAM-type adhesion molecule, is expressed on renal tubular cells, and its increased ectodomain shedding is suggested to contribute to tubular degeneration. A sandwich ELISA for urinary CADM1 was developed using two anti-ectodomain antibodies. Urinary CADM1 concentrations in patients with CKD were measured. Renal biopsy specimens of all patients were pathologically scored for tubulointerstitial lesions using epithelial degeneration, interstitial inflammation, and fibrosis. There was a weak inverse correlation between pathological scores and elevated GFR (eGFR). Notably, this correlation gradually increased in patients with increasing CADM1 concentrations. CADM1 appeared to be a useful marker indicating tubulointerstitial damage from eGFR levels in CKD.

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病では尿細管間質病変の重篤度が残腎機能を規定する。近年、新規尿中バイオマーカーが確立されているが、尿細管間質障害の全体を反映しているとは言い難く、腎生検以外にその重篤度を知るのは難しい。国内で1300万人を超える慢性腎臓病患者の治療においては尿細管間質の慢性炎症とそれに続く線維化を制御する必要性が重要視されているが、国内外の多くの研究にもかかわらず、病態の分子機序、特に慢性炎症の引き金となる上位分子は確定していない。本研究は接着分子結合を介した特異性の高い慢性炎症誘導モデルを提唱しており、極めて独創的かつ重要な課題と認識される。