Thyroid hormones stimulate renal expression of CFTR

Cell Physiol Biochem. 2007;20(1-4):83-90. doi: 10.1159/000104156.

Abstract

CFTR is a multifunctional protein of the ATP binding cassette family that may contribute to overall electrolyte homeostasis by acting as a chloride channel in the kidney. In renal tissues CFTR does not exists only in its full-length form, but also as a kidney-specific, truncated splice variant, TNR-CFTR. In this study we show that both forms of CFTR are regulated by thyroid hormones in rat renal tissue. Four groups of male rats were used: control, hypothyroid, hypothyroid with T(4) treatment and hyperthyroid rats. The hypothyroid rats showed a decrease of both CFTR and TNR-CFTR mRNAs (44%, and 49%, respectively, n=5; p<0.05) and proteins (30% and 37%, respectively, n=5, p<0.05) expressions, compared to control group. In hyperthyroid rats, a significant increase in both CFTR and TRN-CFTR mRNAs expressions (43% and 95%, n=5; p<0.05) and proteins (250% and 38%, respectively, n=5, p<0.05) was observed when compared to control group. Treatment of immortalized rat proximal tubule cells (IRPTC) with T(3) (10(-7)M) produced also an increase of CFTR mRNA expression (95%, n=5, p<0.05). Analysis of the promoter region of CFTR transfected to IRPTC showed that T(3) (10(-7) M) stimulates the CFTR promoter (38%, n=4, p<0.05).

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Primers / genetics
  • Gene Expression / drug effects
  • Hyperthyroidism / genetics
  • Hyperthyroidism / metabolism
  • Hypothyroidism / genetics
  • Hypothyroidism / metabolism
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Thyroid Hormones / metabolism*
  • Thyroxine / blood
  • Thyroxine / pharmacology
  • Transfection
  • Triiodothyronine / pharmacology

Substances

  • CFTR protein, human
  • DNA Primers
  • RNA, Messenger
  • Thyroid Hormones
  • Triiodothyronine
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Thyroxine