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j.kint.2022.04.026.pdf | 3.27 MB | Adobe PDF | 見る/開く |
タイトル: | Lineage tracing analysis defines erythropoietin-producing cells as a distinct subpopulation of resident fibroblasts with unique behaviors |
著者: | Kaneko, Keiichi Sato, Yuki Uchino, Eiichiro Toriu, Naoya Shigeta, Mayo Kiyonari, Hiroshi Endo, Shuichiro Fukuma, Shingo https://orcid.org/0000-0002-8379-8761 (unconfirmed) Yanagita, Motoko https://orcid.org/0000-0002-0339-9008 (unconfirmed) |
著者名の別形: | 金子, 惠一 佐藤, 有紀 内野, 詠一郎 鳥生, 直哉 繁田, 麻葉 清成, 寛 遠藤, 修一郎 福間, 真悟 柳田, 素子 |
キーワード: | erythropoietin renal anemia renal Epo-producing cells (REP cells) renal fibrosis |
発行日: | Aug-2022 |
出版者: | Elsevier BV International Society of Nephrology |
誌名: | Kidney International |
巻: | 102 |
号: | 2 |
開始ページ: | 280 |
終了ページ: | 292 |
抄録: | Erythropoietin (Epo) is produced by a subpopulation of resident fibroblasts in the healthy kidney. We have previously demonstrated that, during kidney fibrosis, kidney fibroblasts including Epo-producing cells transdifferentiate into myofibroblasts and lose their Epo-producing ability. However, it remains unclear whether Epo-producing cells survive and transform into myofibroblasts during fibrosis because previous studies did not specifically label Epo-producing cells in pathophysiological conditions. Here, we generated Epo[CreERT2/+] mice, a novel mouse strain that enables labeling of Epo-producing cells at desired time points and examined the behaviors of Epo-producing cells under pathophysiological conditions. Lineage -labeled cells that were producing Epo when labeled were found to be a small subpopulation of fibroblasts located in the interstitium of the kidney, and their number increased during phlebotomy-induced anemia. Around half of lineage-labeled cells expressed Epo mRNA, and this percentage was maintained even 16 weeks after recombination, supporting the idea that a distinct subpopulation of cells with Epo-producing ability makes Epo repeatedly. During fibrosis caused by ureteral obstruction, Epo[CreERT2/+] -labeled cells were found to transdifferentiate into myofibroblasts with concomitant loss of Epo-producing ability, and their numbers and the proportion among resident fibroblasts increased during fibrosis, indicating their high proliferative capacity. Finally, we confirmed that EpoCreERT2/+-labeled cells that lost their Epo-producing ability during fibrosis regained their ability after kidney repair due to relief of the ureteral obstruction. Thus, our analyses have revealed previously unappreciated characteristic behaviors of Epo-producing cells, which had not been clearly distinguished from those of resident fibroblasts. |
記述: | 腎臓の造血ホルモン、プロの細胞集団が産生. 京都大学プレスリリース. 2022-06-10. Kyoto scientists discover ‘crack team’ of kidney cells that are key to disease recovery. 京都大学プレスリリース. 2022-06-10. |
著作権等: | © 2022 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license. |
URI: | http://hdl.handle.net/2433/275428 |
DOI(出版社版): | 10.1016/j.kint.2022.04.026 |
PubMed ID: | 35644281 |
関連リンク: | https://ashbi.kyoto-u.ac.jp/ja/news/20220609_research-result_yanagita/ https://ashbi.kyoto-u.ac.jp/news/20220609_research-result_yanagita/ |
出現コレクション: | 学術雑誌掲載論文等 |
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