Thyroid hormone stimulates renin gene expression through the thyroid hormone response element

Hiroyuki Kobori, Matsuhiko Hayashi, Takao Saruta

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We previously reported that thyroid hormone stimulates renin synthesis in vivo and in vitro. Here, we analyzed the 5′-flanking sequence of the human renin gene for promoter activity responsive to thyroid hormone using Calu-6 cells, which secrete renin endogenously and express thyroid hormone receptor-β. The luciferase reporter gene was cloned together with 5′-flanking portions of the human renin gene of various lengths into the pGL3-Basic vector. Luciferase activity assays were performed using the Dual Luciferase Reporter Assay System. 3,3′,5-Triiodo-L-thyronine stimulated the promoter activity of pGL3-Basic-1111/+12 and pGL3-Basic-1298/+12 by 2.3±0.1- and 1.7±0.1-fold, respectively. Shorter constructs (pGL3-Basic-144/+12, pGL3-Basic-226/+12, pGL3-Basic-452/+12, and pGL3-Basic-953/+12) were not stimulated by thyroid hormone. These results suggest that there is a possible thyroid hormone response element (5′-AGG TCA GGT CAc aat GTT CCT-3′) between nucleotides -1111 and -953. In 3 constructs with site-directed mutations in this sequence, basal promoter activities were significantly increased, whereas promoter activation by thyroid hormone was abolished. Electrophoretic mobility shift assays showed that the -1111/-953 DNA fragment of the intact human renin gene was bound to nuclear proteins of Calu-6 cells; however, none of the 3 mutant probes were bound to any nuclear proteins. These results suggest that thyroid hormone stimulates the promoter activity of the human renin gene through thyroid hormone response element-dependent mechanisms in Calu-6 cells.

Original languageEnglish
Pages (from-to)99-104
Number of pages6
JournalHypertension
Volume37
Issue number1
Publication statusPublished - 2001

Fingerprint

Response Elements
Thyroid Hormones
Renin
Gene Expression
Luciferases
Nuclear Proteins
Genes
Thyronines
Thyroid Hormone Receptors
5' Flanking Region
Electrophoretic Mobility Shift Assay
Reporter Genes
Human Activities
Nucleotides
Mutation
DNA

Keywords

  • Gene expression
  • Hormones, thyroid
  • Human
  • Renin
  • Response elements

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Thyroid hormone stimulates renin gene expression through the thyroid hormone response element. / Kobori, Hiroyuki; Hayashi, Matsuhiko; Saruta, Takao.

In: Hypertension, Vol. 37, No. 1, 2001, p. 99-104.

Research output: Contribution to journalArticle

Kobori, H, Hayashi, M & Saruta, T 2001, 'Thyroid hormone stimulates renin gene expression through the thyroid hormone response element', Hypertension, vol. 37, no. 1, pp. 99-104.
Kobori, Hiroyuki ; Hayashi, Matsuhiko ; Saruta, Takao. / Thyroid hormone stimulates renin gene expression through the thyroid hormone response element. In: Hypertension. 2001 ; Vol. 37, No. 1. pp. 99-104.
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