Int J Biol Sci 2015; 11(2):122-132. doi:10.7150/ijbs.10773 This issue

Research Paper

Stanniocalcin-1 Controls Ion Regulation Functions of Ion-transporting Epithelium Other than Calcium Balance

Ming-Yi Chou1,2, Chia-Hao Lin1, Pei-Lin Chao1, Jo-Chi Hung1, Shelly A. Cruz1, Pung-Pung Hwang1✉

1. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
2. RIKEN Brain Science Institute, Laboratory for Developmental Gene Regulation, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.

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Chou MY, Lin CH, Chao PL, Hung JC, Cruz SA, Hwang PP. Stanniocalcin-1 Controls Ion Regulation Functions of Ion-transporting Epithelium Other than Calcium Balance. Int J Biol Sci 2015; 11(2):122-132. doi:10.7150/ijbs.10773. Available from

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Graphic abstract

Stanniocalcin-1 (STC-1) was first identified to involve in Ca2+ homeostasis in teleosts, and was thought to act as a hypocalcemic hormone in vertebrate. Recent studies suggested that STC-1 exhibits broad effects on ion balance, not confines to Ca2+, but the mechanism of this regulation process remains largely unknown. Here, we used zebrafish embryos as an alternative in vivo model to investigate how STC-1 regulates transepithelial ion transport function in ion-transporting epithelium. Expression of stc-1 mRNA in zebrafish embryos was increased in high-Ca2+ environments but decreased by acidic and ion-deficient treatments while overexpression of stc-1 impaired the hypotonic acclimation by decreasing whole body Ca2+, Na+, and Cl- contents and H+ secretion ability. Injection of STC-1 mRNA also down-regulated mRNA expressions of epithelial Ca2+ channel, H+-ATPase, and Na+-Cl- cotransporter, suggesting the roles of STC-1 in regulation of ions other than Ca2+. Knockdown of STC-1 caused an increase in ionocyte progenitors (foxi3a as the marker) and mature ionocytes (ion transporters as the markers), but did not affect epithelium stem cells (p63 as the marker) in the embryonic skin. Overexpression of STC-1 had the corresponding opposite effect on ionocyte progenitors, mature ionocytes in the embryonic skin. Taken together, STC-1 negatively regulates the number of ionocytes to reduce ionocyte functions. This process is important for body fluid ionic homeostasis, which is achieved by the regulation of ion transport functions in ionocytes. The present findings provide new insights into the broader functions of STC-1, a hypocalcemic hormone.

Keywords: stanniocalcin, ion regulation, differentiation, ionocyte, zebrafish.