Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis

in Journal of Endocrinology
Authors:
Shang-Wu Shih Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
Department of Life Science, National Taiwan University, Taipei, Taiwan

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https://orcid.org/0000-0002-2620-1340
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Jia-Jiun Yan Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

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Yi-Hsing Wang Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

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Yi-Ling Tsou Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

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Ling Chiu Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
Department of Life Science, National Taiwan University, Taipei, Taiwan

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Yung-Che Tseng Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

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Ming-Yi Chou Department of Life Science, National Taiwan University, Taipei, Taiwan

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Pung-Pung Hwang Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
Department of Life Science, National Taiwan University, Taipei, Taiwan

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Correspondence should be addressed to P-P Hwang: pphwang@gate.sinica.edu.tw
DOI:
https://doi.org/10.1530/JOE-21-0112
Volume/Issue:
Volume 251: Issue 2
Article Type:
Research Article
Page Range:
149–159
Online Publication Date:
22 Oct 2021
Copyright:
© Society for Endocrinology 2021
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Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that Errγ2 may play a crucial role in ion uptake. In situ hybridization showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl− transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl− cotransporter (Ncc), the number of Ncc ionocytes, Na+/Cl− influxes of ionocytes, and whole-body Na+/Cl− contents. In FW with low Na+ and low Cl−, the expression levels of mRNA for Na+/H+ exchanger 3 (Nhe3) and Ncc were both decreased in Errγ2 morphants. Treating embryos with DY131, an agonist of Errγ, increased the whole-body Na+/Cl− contents and ncc mRNA expression in Errγ2 morphants. As such, medaka Errγ2 may control Na+/Cl− uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

Supplementary Materials

    • Supplementary Table 1. Primer sets used for qRT-PCR and ISH.
    • Supplementary Table 2. Statistical analysis of one-way ANOVA.
    • Supplementary Figure 1. Survival of the ERRγ2 morphants. The survival probability of 1-7 dpf embryos after injection of 1, 2, and 4 ng ERRγ2 MO is shown.
    • Supplementary Figure 2. Effects of ERRγ2 knockdown on whole-body Ca2+ content in FW-acclimated embryos. Fertilized eggs were first injected with ERRγ2 MO. Then, embryos were dechorionated at 5 dpf. Whole-body Ca2+ content was measured at 6 dpf. Bars represent the mean ± SD. Sample size is shown in the parentheses. One-way ANOVA, Tukey’s pair-wise comparison. Same letters indicate no significant difference between groups.
    • Supplementary Figure 3 Expression analysis of ERRγ2 protein after ERRγ2 knockdown. The expression of ERRγ2 protein in 3 and 6 dpf ERRγ2 morphants was analyzed by western blot. The blots showed bands at molecular weights corresponding to ERRγ2 and actin; approximately 55 kDa and 43 kDa, respectively (A and C). The expression of ERRγ2 protein was quantified and normalized to actin (B and D). Bars represent the mean ± SD. Sample size is shown in the parentheses. One-way ANOVA Tukey’s pair-wise comparison. Different letters indicate a significant difference between groups, p < 0.05. Same letters indicate no significant difference between groups.
    • Supplementary Figure 4. Effects of different concentrations of DY131 treatment on the whole-body Cl content in FW-acclimated embryos. Embryos were dechorionated at 4 dpf and treated with 0 (FW), 10, 30, and 50 μM DY131 for 24 hr. Then, the whole-body Cl content was measured. Treatment with 50 μM DY131 for 24 hr significantly increased the Cl content compared to the 0 μM DY131 (FW) group. Bars represent the mean ± SD. Sample size is shown in the parentheses. One-way ANOVA, Tukey’s pair-wise comparison. Different letters indicate a significant difference between groups, p < 0.05. Same letters indicate no significant difference between groups.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
11
Article Type:
Research Article
Received Date:
26 Aug 2021
Accepted Date:
08 Sep 2021
Print Publication Date:
01 Nov 2021
Online Publication Date:
22 Oct 2021
Keywords:
estrogen-related receptor; NaCl uptake; Ncc; Nhe; euryhaline fish

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