佐藤 有紀

Last Update: 2019/06/24 16:10:11

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Name(Kanji/Kana/Abecedarium Latinum)
佐藤 有紀/サトウ ユウキ/Sato, Yuki
Primary Affiliation(Org1/Job title)
Graduate Schools Medicine/Program-Specific Assistant Professor
Academic Degree
Field(Japanese) Field(English) University(Japanese) University(English) Method
博士(医学) 京都大学
researchmap URL
https://researchmap.jp/7000011398
Research Topics
(Japanese)
高齢者腎臓病の病態生理の解明
(English)
Pathophysiology of kidney disease in the elderly
Overview of the research
(Japanese)
近年先進国を中心に末期腎不全患者は増加の一途を辿っているが、その多くが高齢者である。高齢者が末期腎不全に至る主たる原因は急性腎障害(AKI:Acute Kidney Injury)であることが疫学研究より示されている。AKIは脱水や敗血症などを原因として発症する日常的に遭遇する頻度の高い病態であるにも関わらず、その病態生理には不明な点が多い。また若年者のAKIは回復傾向を認める症例が多いのに対して、高齢者のAKIは回復傾向を認めず重度の慢性腎臓病(CKD:chronic kidney disease)や末期腎不全へと進展する症例が多いことも明らかにされつつあるが、なぜ加齢に伴いAKIからの回復が悪くなるのかについても不明であった。最近我々は複数のAKIモデルを用いた検討で、若齢個体では組織修復が起こる時期に高齢個体では三次リンパ組織が誘導され、そこでリンパ球の活性化が起こり炎症を遷延・増悪させることを見出した。さらにこの三次リンパ組織の形成・維持には多彩な性質を獲得した同一系譜の線維芽細胞がparacrine interactionなどを介し重要な役割を担うこと、三次リンパ組織を標的とした治療法が腎予後を改善する可能性を見出している。
(English)
There has been a worldwide increase in the number of patients with end-stage renal disease (ESRD), predominantly in the elderly population in developed countries. Clinical studies demonstrated that the elderly show a reduced capacity for renal regeneration after acute kidney injury (AKI) and often progress to ESRD, yet the precise mechanism remains unclear. AKI is a very common clinical condition defined as a rapid fall in renal function, often as a result of an ischemic or nephrotoxic renal insults. Recently, we have demonstrated that aged mice developed multiple tertiary lymphoid tissues (TLTs) after AKI, whereas young mice did not. We also demonstrated that resident fibroblasts from a single lineage diversified into fibroblasts with distinct phenotypes, including p75 neurotrophin receptor (p75NTR) expressing fibroblasts, retinoic acid producing fibroblasts and homeostatic chemokine producing fibroblasts, all of which underlie TLT formation. Interventions with anti-CD4 monoclonal antibody as well as dexamethasone abolished TLTs and improved renal outcomes. TLTs were also observed in aged human kidneys, whose cellular and molecular components were similar to those of mouse TLTs. Thus, TLTs represent a novel therapeutic target of AKI in the elderly.
Fields of research (key words)
Key words(Japanese) Key words(English)
急性腎障害、三次リンパ組織、線維芽細胞、老化、免疫老化 Acute kidney injury, tertiary lymphoid tissue, fibroblasts, immunosenescence
Published Papers
Author Author(Japanese) Author(English) Title Title(Japanese) Title(English) Bibliography Bibliography(Japanese) Bibliography(English) Publication date Refereed paper Language Publishing type Disclose
Yuki Sato 佐藤 有紀 Yuki Sato Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney 多様な線維芽細胞が加齢に伴う腎臓の3次リンパ組織形成に関わる Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney Journal of Clinical Investigation Insight, 1, 11, e87680-e87680 Journal of Clinical Investigation Insight, 1, 11, e87680-e87680 Journal of Clinical Investigation Insight, 1, 11, e87680-e87680 2016/07 Refereed English Research paper(scientific journal) Disclose to all
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Awards
Title(Japanese) Title(English) Organization name(Japanese) Organization name(English) Date
日本抗加齢医学会研究奨励賞 Young Scientist Award for Anti-Aging Medicine 日本抗加齢医学会 Japanese Society of Anti-Aging Medicine 2019/06/16
第61回日本腎臓学会学術総会Best English Presentation Award Best English Presentation Award 日本腎臓学会 Japanese Society of Nephrology 2018/06/09
日本臨床分子医学会学学術奨励賞 日本臨床分子医学会 Japanese Society of Molecular Medicine 2018/04/14
第39回分子生物学会 優秀ポスター賞 日本分子生物学会 The Molecular Biology Society of Japan 2016/12/01
第38回日本炎症・再生医学会 優秀演題賞 日本炎症・再生医学会 The Japanese Society of Inflammation and Regeneration 2017/07/19
External funds: competitive funds and Grants-in-Aid for Scientific Research (Kakenhi)
Type Position Title(Japanese) Title(English) Period
若手研究(B) Representative 高齢者腎臓病の予後不良因子、三次リンパ組織を検出する新規バイオマーカーの開発 (平成29年度分) 2017/04/01-2018/03/31
若手研究(B) Representative 高齢者腎臓病の予後不良因子、三次リンパ組織を検出する新規バイオマーカーの開発 (平成30年度分) 2018/04/01-2019/03/31
Activities at international organization(s)
Activity(Japanese) Activity(English) Organization name Period
講演・研究活動 Invited talk (Visiting Professor) Rammelkamp Center for Education and Research, The MetroHealth System, Case Western Reserve University Affiliate, Cleaveland, Ohio, USA 2016/11/14-2016/11/14
講演・研究活動 Invited talk Department of Nephrology, RWTH University of Aachen, Aachen, Germany 2018/05/22-2018/05/22
講演・研究活動 Seminar Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany. 2018/05/29-2018/05/29