The role of Pericyte Senescence in Diabetic Complications
| Project/Area Number |
20H03572
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
越坂 理也 千葉大学, 医学部附属病院, 助教 (30466700)
加藤 尚也 千葉大学, 医学部附属病院, 助教 (90841974)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 細胞老化 / 線維化 / 老化 / 線維芽細胞 / ポドサイト / 尿細管細胞 / Pericyte / Werner症候群 |
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| Outline of Research at the Start |
近年、血管壁Pericyte（周皮細胞）が、形質転換により組織の線維化や炎症を制御することが報告され、糖尿病合併症の病態形成においてもPericyteの機能異常が示唆されている。しかしながら、高齢糖尿病患者のPericyte障害における老化の関与については、未だ不明である。そこで本研究では、高齢糖尿病患者の血管合併症における、Pericyte老化の役割とその機序を明らかにする。この目的のために、遺伝子改変マウス、や早老症iPS細胞由来のオルガノイドを用いたPericyteの機能解析を行い、さらに高齢糖尿病患者のPericyteにおける遺伝子発現変化と臨床指標との関連を解析する。
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| Outline of Final Research Achievements |
In this study, we analyzed the role of the transcription factor Tcf21 in cardiac fibrosis, that is often observed in the elderly people. We found that Tcf21 regulates cell proliferation and matrix expression via Pdgf receptor pathway, and functions to promote fibrosis, at least in embryonic fibroblasts. We also examined kidney aging and fibrosis, and found that fibrosis is promoted in aged mice and aged diabetic mice, with increased extracellular matrix expression, altered glomerular structure, decreased vascular distribution, and cellular senescence. Single cell analysis showed that fibroblast migration and Tgfb signaling in fibroblast and pericytes are involved in the background of this fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、心臓と腎臓における、加齢に伴う線維化の機序解明を行っている。腎臓においては老化に伴う線維化や血管の減少を捕捉し、高齢マウスを用いたシングルセル解析まで到達した。今までの高齢個体の腎臓のシングルセル解析は尿細管を対象とした解析がほとんどであり、本検討により頻度の低い細胞種における老化の役割が解明できると期待される。
また、本検討によって得られる老化に伴う線維化の基盤情報は、腎臓の線維化のみならず多くの加齢関連疾患に共通するメカニズム解明につながり、加齢関連疾患に共通する治療方法へのブレークスルーをもたらす可能性がある。
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Report
(3 results)
Research Products
(44 results)
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[Journal Article] Quality of life in Werner syndrome and associated subjective foot/ankle symptoms: A cross-sectional survey2022
Author(s)
Kitagawa, Y., Amemiya, A., Ogata, H., Koshizaka, M., Shoji, M., Maezawa, Y., Akita, S., Mitsukawa, N., Yokote, K.
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Journal Title
Geriatrics & Gerontology International
Volume: 23(3)
Issue: 3
Pages: 188-193
DOI
Related Report
Peer Reviewed
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[Journal Article] RNaseH2A downregulation drives inflammatory gene expression via genomic DNA fragmentation in senescent and cancer cells2022
Author(s)
Sugawara S, Okada R, Loo TM, Tanaka H, Miyata K, Chiba M, Kawasaki H, Katoh K, Kaji S, Maezawa Y, Yokote K, Nakayama M, Oshima M, Nagao K, Obuse C, Nagayama S, Takubo K, Nakanishi A, Kanemaki MT, Hara E, Takahashi A.
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Journal Title
Commun Biol
Volume: 5
Issue: 1
Pages: 1420-1420
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fibroblasts from different body parts exhibit distinct phenotypes in adult progeria Werner syndrome2021
Author(s)
Kato H, Maezawa Y, Takayama N, Ouchi Y, Kaneko H, Kinoshita D, Takada-Watanabe A, Oshima M, Koshizaka M, Ogata H, Kubota Y, Mitsukawa N, Eto K, Iwama A, Yokote K.
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Journal Title
Aging (Albany NY)
Volume: 13
Issue: 4
Pages: 4946-4961
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Time gap between the onset and diagnosis in Werner syndrome: a nationwide survey and the 2020 registry in Japan2020
Author(s)
Koshizaka M, Maezawa Y, Maeda Y, Shoji M, Kato H, Kaneko H, Ishikawa T, Kinoshita D, Kobayashi K, Kawashima J, Sekiguchi A, Motegi SI, Nakagami H, Yamada Y, Tsukamoto S, Taniguchi A, Sugimoto K, Shoda Y, Hashimoto K, Yoshimura T, Suzuki D, Kuzuya M, Takemoto M, Yokote K.
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Journal Title
Aging
Volume: 12
Issue: 24
Pages: 24940-24956
DOI
Related Report
Peer Reviewed / Open Access
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