{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:27:29Z","timestamp":1777498049147,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["26461259"],"award-info":[{"award-number":["26461259"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["16K09654"],"award-info":[{"award-number":["16K09654"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["16K19493"],"award-info":[{"award-number":["16K19493"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["16K08505"],"award-info":[{"award-number":["16K08505"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["17K16578"],"award-info":[{"award-number":["17K16578"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["18K08247"],"award-info":[{"award-number":["18K08247"]}]},{"name":"a Grant-in Aid for Scientific Research from the Ministry of 339 Education, Culture, Sports, Sciences and Technology of Japan","award":["19K09226"],"award-info":[{"award-number":["19K09226"]}]},{"name":"the Science Research Promotion Fund from the Promotion, Kitasato University Medical Center","award":["H25-003"],"award-info":[{"award-number":["H25-003"]}]},{"name":"the Science Research Promotion Fund from the Promotion, Kitasato University Medical Center","award":["H24-011"],"award-info":[{"award-number":["H24-011"]}]},{"DOI":"10.13039\/501100012359","name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","doi-asserted-by":"publisher","award":["2015"],"award-info":[{"award-number":["2015"]}],"id":[{"id":"10.13039\/501100012359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["DK119793"],"award-info":[{"award-number":["DK119793"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo production following the administration of these drugs have not been identified. We developed a novel method for the detection of the Epo protein that employs deglycosylation-coupled Western blotting. With protein deglycosylation, tissue Epo contents can be quantified over an extremely wide range. Using this method, we examined the effects of the PHD inhibitor, Roxadustat (ROX), and severe hypoxia on Epo production in various tissues in rats. We observed that ROX increased Epo mRNA expression in both the kidneys and liver. However, Epo protein was detected in the kidneys but not in the liver. Epo protein was also detected in the salivary glands, spleen, epididymis and ovaries. However, both PHD inhibitors (ROX) and severe hypoxia increased the Epo protein abundance only in the kidneys. These data show that, while Epo is produced in many tissues, PHD inhibitors as well as severe hypoxia regulate Epo production only in the kidneys.<\/jats:p>","DOI":"10.3390\/molecules27031119","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:37:48Z","timestamp":1644363468000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Roxadustat on Erythropoietin Production in the Rat Body"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9380-1653","authenticated-orcid":false,"given":"Yukiko","family":"Yasuoka","sequence":"first","affiliation":[{"name":"Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-9619","authenticated-orcid":false,"given":"Yuichiro","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Fukuyama","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Omiya","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Iwate, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truyen D.","family":"Pham","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-0883","authenticated-orcid":false,"given":"Taiga","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noritada","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Shimada","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Nagaba","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Iwate, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Mukoyama","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4441-0306","authenticated-orcid":false,"given":"Yuichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Wall","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-0607","authenticated-orcid":false,"given":"Jeff M.","family":"Sands","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB Room 3313, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1025-1690","authenticated-orcid":false,"given":"Noriko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsumasa","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-7380","authenticated-orcid":false,"given":"Hiroshi","family":"Nonoguchi","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto 364-8501, Saitama, 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