Thyroid hormone modulates CIC-2 chloride channel gene expression in rat renal proximal tubules

D. Santos Ornellas, R. Grozovsky, R. C. Goldenberg, D. P. Carvalho, P. Fong, W. B. Guggino, M. Morales

Research output: Contribution to journalArticle

Abstract

Thyroid hormones has its main role in controlling metabolism, but it can also modulate extracellular fluid volume (ECFV) through its action on the expression and activity of Na+ transporters. Otherwise, chloride is the main anion in the ECFV and the influence of thyroid hormones in the regulation of chloride transporters is not yet understood. In this work, we studied the effect of thyroid hormones in the expression of ClC-2, a cell volume-, pH- and voltage-sensitive Cl- channel, in rat kidney. To analyze the modulation of ClC-2 gene expression by thyroid hormones, we used hypothyroid (Hypo) rats with or without thyroxine (T4) replacement and hyperthyroid (Hyper) rats as our experimental models. Total RNA was isolated and the expression of ClC-2 mRNA was evaluated by a ribonuclease protection assay, and/or semi-quantitative RT-PCR. Renal ClC-2 expression decreased in Hypo rats and increased in Hyper rats. In addition, semiquantitative RT-PCR of different nephron segments showed that these changes were due exclusively to the modulation of ClC-2 mRNA expression by thyroid hormone in convoluted and straight proximal tubules. To investigate whether thyroid hormones action was direct or indirect, renal proximal tubule primary culture cells were prepared and subjected to different T4 concentrations. ClC-2 mRNA expression was increased by T4 in a dose-dependent fashion, as analyzed by RT-PCR. Western blotting demonstrated that ClC-2 protein expression followed the same profile of mRNA expression.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
JournalJournal of Endocrinology
Volume178
Issue number3
DOIs
StatePublished - Sep 1 2003

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Santos Ornellas, D., Grozovsky, R., Goldenberg, R. C., Carvalho, D. P., Fong, P., Guggino, W. B., & Morales, M. (2003). Thyroid hormone modulates CIC-2 chloride channel gene expression in rat renal proximal tubules. Journal of Endocrinology, 178(3), 503-511. https://doi.org/10.1677/joe.0.1780503