2. Academic Validation
  3. Fludrocortisone stimulates erythropoietin production in the intercalated cells of the collecting ducts

Fludrocortisone stimulates erythropoietin production in the intercalated cells of the collecting ducts

  • Biochem Biophys Res Commun. 2018 Sep 18;503(4):3121-3127. doi: 10.1016/j.bbrc.2018.08.102.
Yukiko Yasuoka 1,  Yuichiro Izumi 2,  Takanori Nagai 3,  Takashi Fukuyama 4,  Yushi Nakayama 2,  Hideki Inoue 2,  Kahori Horikawa 3,  Miho Kimura 3,  Masayoshi Nanami 3,  Kengo Yanagita 5,  Tomomi Oshima 1,  Taiga Yamazaki 4,  Takayuki Uematsu 4,  Rui Yamamura 4,  Noritada Kobayashi 4,  Yoshitaka Shimada 6,  Yasushi Nagaba 6,  Takeshi Nakanishi 3,  Tetsuro Yamashita 7,  Masashi Mukoyama 2,  Yuichi Sato 5,  Katsumasa Kawahara 1,  Hiroshi Nonoguchi 8
Affiliations

Affiliations

  • 1 Department of Physiology, Kitasato University, School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
  • 2 Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
  • 3 Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
  • 4 Division of Biomedical Research, Kitasato University Medical Center, 6-100 Arai, Kitamoto, Saitama, 364-8501, Japan.
  • 5 Department of Molecular Diagnostics, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
  • 6 Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto, Saitama, 364-8501, Japan.
  • 7 Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate, 020-8550, Japan.
  • 8 Division of Internal Medicine, Kitasato University Medical Center, 6-100 Arai, Kitamoto, Saitama, 364-8501, Japan. Electronic address: [email protected].
PMID: 30146260 DOI: 10.1016/j.bbrc.2018.08.102
Abstract

Erythropoietin has been thought to be secreted to plasma soon after the production because of the difficulty of Western blot analysis and immunohistochemistry. We established the new methods of Western blot analysis and immunohistochemistry. Using the new methods, we investigated the effects of aldosterone and fludrocortisone, an analogue of aldosterone on erythropoietin mRNA and protein production by the kidneys. Aldosterone stimulated Epo and HIF2α mRNA expressions in tubule suspensions and microdissected medullary thick ascending limbs and outer medullary collecting ducts. Western blot analysis showed a recombinant erythropoietin at 34-45 kDa and kidney erythropoietin at 36-40 and 42 kDa, both of which shifted to 22 kDa by deglycosylation. Erythropoietin protein expression was observed in the nephrons but not in the interstitial cells in control condition. Fludrocortisone stimulated erythropoietin mRNA and protein expressions in the distal nephrons, particularly in the intercalated cells of the collecting ducts. These data show that erythropoietin is produced by the nephrons by the regulation of renin-angiotensin-aldosterone system and not by the renal interstitial cells in control condition.

Keywords

Collecting ducts; Deglycosylation; Erythropoietin; Hypoxia; Interstitial cells; Renin-angiotensin-aldosterone system.

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