論文 - 詳細
| RRC ID | 45076 |
|---|---|
| 著者 | Nagai T, Yasuoka Y, Izumi Y, Horikawa K, Kimura M, Nakayama Y, Uematsu T, Fukuyama T, Yamazaki T, Kohda Y, Hasuike Y, Nanami M, Kuragano T, Kobayashi N, Obinata M, Tomita K, Tanoue A, Nakanishi T, Kawahara K, Nonoguchi H. |
| タイトル | Reevaluation of erythropoietin production by the nephron. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Erythropoietin production has been reported to occur in the peritubular interstitial fibroblasts in the kidney. Since the erythropoietin production in the nephron is controversial, we reevaluated the erythropoietin production in the kidney. We examined mRNA expressions of erythropoietin and HIF PHD2 using high-sensitive in situ hybridization system (ISH) and protein expression of HIF PHD2 using immunohistochemistry in the kidney. We further investigated the mechanism of erythropoietin production by hypoxia in vitro using human liver hepatocell (HepG2) and rat intercalated cell line (IN-IC cells). ISH in mice showed mRNA expression of erythropoietin in proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs) and cortical collecting ducts (CCDs) but not in the peritubular cells under normal conditions. Hypoxia induced mRNA expression of erythropoietin largely in peritubular cells and slightly in PCTs, DCTs, and CCDs. Double staining with AQP3 or AE1 indicated that erythropoietin mRNA expresses mainly in β-intercalated or non α/non β-intercalated cells of the collecting ducts. Immunohistochemistry in rat showed the expression of HIF PHD2 in the collecting ducts and peritubular cells and its increase by anemia in peritubular cells. In IN-IC cells, hypoxia increased mRNA expression of erythropoietin, erythropoietin concentration in the medium and protein expression of HIF PHD2. These data suggest that erythropoietin is produced by the cortical nephrons mainly in the intercalated cells, but not in the peritubular cells, in normal hematopoietic condition and by mainly peritubular cells in hypoxia, suggesting the different regulation mechanism between the nephrons and peritubular cells. |
| 巻・号 | 449(2) |
| ページ | 222-8 |
| 公開日 | 2014-6-27 |
| DOI | 10.1016/j.bbrc.2014.05.014 |
| PII | S0006-291X(14)00859-6 |
| PMID | 24832733 |
| MeSH | Animals Cell Hypoxia Cell Line Erythropoietin / biosynthesis* Erythropoietin / genetics Gene Expression Regulation Hep G2 Cells Humans Hypoxia-Inducible Factor-Proline Dioxygenases / genetics Hypoxia-Inducible Factor-Proline Dioxygenases / metabolism Immunohistochemistry In Situ Hybridization Kidney / cytology Kidney / metabolism Mice Mice, Inbred C57BL Nephrons / metabolism* Procollagen-Proline Dioxygenase / genetics Procollagen-Proline Dioxygenase / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Tissue Distribution |
| IF | 2.985 |
| 引用数 | 14 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 |