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タイトル: | Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice |
著者: | Asada, Nariaki Takase, Masayuki Nakamura, Jin Oguchi, Akiko Asada, Misako Suzuki, Norio Yamamura, Ken-ichi Nagoshi, Narihito Shibata, Shinsuke Rao, Tata Nageswara Fehling, Hans Joerg Fukatsu, Atsushi Minegishi, Naoko Kita, Toru Kimura, Takeshi Okano, Hideyuki Yamamoto, Masayuki Yanagita, Motoko |
発行日: | 12-Sep-2011 |
出版者: | American Society for Clinical Investigation |
引用: | Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, Yamamura K, Nagoshi N, Shibata S, Rao TN, Fehling HJ, Fukatsu A, Minegishi N,8, Kita T, Kimura T, Okano H, Yamamoto M, Yanagita M. Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest. 2011; doi:10.1172/JCI57301; Published September 12, 2011. |
誌名: | Journal of Clinical Investigation |
巻: | 121 |
号: | 10 |
開始ページ: | 3981 |
終了ページ: | 3990 |
抄録: | In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero–Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage- labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia. |
記述: | 慢性腎臓病の2大合併症である腎臓の線維化と腎性貧血のメカニズムの解明. 京都大学プレスリリース. 2011-09-13. |
著作権等: | © 2011, The American Society for Clinical Investigation. |
URI: | http://hdl.handle.net/2433/147049 |
DOI(出版社版): | 10.1172/JCI57301 |
PubMed ID: | 21911936 |
関連リンク: | https://www.kyoto-u.ac.jp/static/ja/news_data/h/h1/news6/2011/110913_1.htm http://www.jci.org/articles/view/57301/pdf |
出現コレクション: | 学術雑誌掲載論文等 |
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