THYROID-HORMONE STIMULATES NA+-K+-ATPASE GENE-EXPRESSION IN CULTURED RAT MESANGIAL CELLS

Thyroid hormone 3,3',5-triiodothyronine (T3) is an important regulator of Na+-K+adenosinetriphosphatase (Na+-K+-ATPase) activity in a variety of mammalian target tissues. In the present study, we examined the expression of Na+-K+-ATPase alpha- and beta-subunit mRNAs by T3 in cultured rat mesangial cells. Northern blot analysis of total RNA isolated from cultured rat mesangial cells revealed the expression of mRNAs encoding Na+-K+-ATPase alpha1- and beta1-subunits; mRNAs encoding alpha2- and alpha3-subunits were undetectable. Exposure of mesangial cells to T3 (10(-8) M) caused a threefold increase in the alpha1-mRNA expression, which was first detected at 6 h and sustained for at least 48 h. The beta1-mRNA expression was gradually increased by T3, with a maximum fourfold elevation at 48 h. The 50% effective concentration (EC50) for the alpha1- and beta1-mRNA induction by T3 was approximately 10(-10) M. The half-life of alpha1-mRNA analyzed by actinomycin D chase was approximately 3 h and was not affected by T3. The augmented alpha1-mRNA expression by T3 was associated with a 2.4-fold increase in the alpha1-subunit protein accumulation and a 1.6-fold increase in Na+-K+-ATPase activity. These data suggest that thyroid hormone stimulates Na+-K+-ATPase gene expression, protein accumulation, and enzyme activity in rat mesangial cells.