Thyroid hormones stimulate renal expression of CFTR.
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).
de Andrade Pinto
Ana C O
AC
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Barbosa
Carolina M L
CM
Ornellas
Debora S
DS
Novaira
Horacio J
HJ
de Souza-Menezes
Jackson
J
Ortiga-Carvalho
Tania M
TM
Fong
Peying
P
Morales
Marcelo M
MM
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006980:Hyperthyroidism / Q000235:genetics / Q000378:metabolism; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology
C505032:CFTR protein, human; D017931:DNA Primers; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D013974:Thyroxine