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Journal of the American Society of Nephrology, Vol 2, 1360-1367, Copyright © 1992 by American Society of Nephrology

REGULAR ARTICLES

Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells

JS Chan, AH Chan, ZR Nie, R Sikstrom, S Lachance, S Hashimoto and S Carriere
University of Montreal, Maisonneuve-Rosemont Hospital, Research Center, Quebec, Canada.

Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N- 1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N- 53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0-, 12-, and 2.5- fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(- 7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N- 35/+18).(ABSTRACT TRUNCATED AT 250 WORDS)


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