Kidney Week

Abstract: FR-PO473

Fludrocortisone Stimulates Erythropoietin (Epo) Protein Expression in the Distal Tubules of Mouse Kidney

Session Information

• Anemia and Iron Metabolism: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 201 Anemia and Iron Metabolism: Basic

Authors

• Yasuoka, Yukiko, Kitasato University, School of Medicine, Sagamihara, Kanagawa, Japan

Yukiko Yasuoka,

• Oshima, Tomomi, Kitasato University, School of Medicine, Sagamihara, Kanagawa, Japan

Tomomi Oshima,

• Izumi, Yuichiro, Kumamoto University, Kumamoto, Japan

Yuichiro Izumi,

• Sato, Yuichi, Kitasato University, School of Allied Health Sciences, Sagamihara, Japan

Yuichi Sato,

• Takahashi, Noriko, Kitasato University, School of Medicine, Sagamihara, Kanagawa, Japan

Noriko Takahashi,

• Nonoguchi, Hiroshi, Kitasato University Medical Center, Kitamoto, Saitama, Japan

Hiroshi Nonoguchi,

• Kawahara, Katsumasa, Kitasato University, School of Medicine, Sagamihara, Kanagawa, Japan

Katsumasa Kawahara,

Background

Although normal plasma Epo concentration is very low, Epo mRNA was expressed in the kidney tubules under normal condition (Nagai, Yasuoka, et al, 2014). We further showed that fludrocortisone, an aldosterone receptor agonist, stimulated Epo mRNA expression in the distal nephron (Yasuoka, et al, ASN 2017). In this study, we investigated the localization of Epo protein-producing cells in the kidney and liver after fludrocortisone injection.

Methods

Fludrocortisone (2.5 mg/100 g BW) or Angiotensin II (0.5 µg/100 g BW) was once applied to mice (C57BL/6J, male, 10 weeks). After 2, 4, 6 and 72 hr, kidneys were examined by Western blot and immunohistochemistry using anti-Epo antibodies.

Results

Under normal (basal) conditions, Epo staining was widely found along the nephron (proximal tubules < thick ascending limbs < collecting ducts). Fludrocortisone significantly increased Epo production in the medullary thick ascending limb, and cortical and outer medullary collecting ducts, particularly in type A of intercalated cells after 4-6 hr. Western blot showed that Epo protein expression was increased by 5-fold in the kidney but not changed in the liver. Angiotensin II stimulated Epo mRNA expression in proximal and distal tubules but not in the interstitial cells. Epo staining decreased to the basal level after 72 hr, but was not detected in the interstitial cells.

Conclusion

Renin-angiotensin-aldosterone system regulates Epo production by the nephron.

Funding

• Government Support - Non-U.S.