TY - JOUR
T1 - Thyroid hormone receptor-dependent transcriptional regulation of fibrinogen and coagulation proteins
AU - Shih, Chung Hsuan
AU - Chen, Shen Liang
AU - Yen, Chun Che
AU - Huang, Y. A.Hui
AU - Chen, Chi D.E.
AU - Lee, Yun Shien
AU - Lin, Kwang Huei
PY - 2004/6
Y1 - 2004/6
N2 - Thyroid hormone (T3) regulates growth, development, and differentiation. These activities are mediated by the nuclear thyroid hormone receptors (TRs), which belong to the steroid/TR superfamily of ligand-dependent transcription factors. The effect of T3 treatment on target gene regulation was investigated in a TRα-overexpressing hepatoma cell line (HepG2-TRα), by performing cDNA microarrays. We demonstrate that 148 of the 7597 genes represented were up-regulated by T3, including fibrinogen and several other components of the coagulation factor system. To confirm the microarray results, fibrinogen and a small number of the blood clotting components were further investigated using quantitative RT-PCR. The T3-induction ratios observed with quantitative RT-PCR for factors such as thrombin (8-fold), coagulation factor X (4.9-fold), and hepatoglobin (30-fold) were similar to those observed by the cDNA microarray analysis. Further investigation, using HepG2-TRα (cell lines, revealed a 2- to 3-fold induction of fibrinogen transcription after 24 h of T3 treatment. In addition, T3 treatment increased the level of fibrinogen protein expression 2.5- to 6-fold at 48 h. The protein synthesis inhibitor, cycloheximide, did not inhibit the induction of fibrinogen by T 3, indicating that this regulation was direct. Furthermore, transcription run-on experiments indicate that the induction of fibrinogen by T3 is regulated largely at the level of transcription. Similar observations were made on the regulation of fibrinogen by T3 using rats that received surgical thyroidectomy (TX) as an in vivo model. These results suggest that T3 plays an important role in the process of blood coagulation and inflammation and may contribute to the understanding of the association between thyroid diseases and the misregulation of the inflammatory and clotting profile evident in the circulatory system of these patients.
AB - Thyroid hormone (T3) regulates growth, development, and differentiation. These activities are mediated by the nuclear thyroid hormone receptors (TRs), which belong to the steroid/TR superfamily of ligand-dependent transcription factors. The effect of T3 treatment on target gene regulation was investigated in a TRα-overexpressing hepatoma cell line (HepG2-TRα), by performing cDNA microarrays. We demonstrate that 148 of the 7597 genes represented were up-regulated by T3, including fibrinogen and several other components of the coagulation factor system. To confirm the microarray results, fibrinogen and a small number of the blood clotting components were further investigated using quantitative RT-PCR. The T3-induction ratios observed with quantitative RT-PCR for factors such as thrombin (8-fold), coagulation factor X (4.9-fold), and hepatoglobin (30-fold) were similar to those observed by the cDNA microarray analysis. Further investigation, using HepG2-TRα (cell lines, revealed a 2- to 3-fold induction of fibrinogen transcription after 24 h of T3 treatment. In addition, T3 treatment increased the level of fibrinogen protein expression 2.5- to 6-fold at 48 h. The protein synthesis inhibitor, cycloheximide, did not inhibit the induction of fibrinogen by T 3, indicating that this regulation was direct. Furthermore, transcription run-on experiments indicate that the induction of fibrinogen by T3 is regulated largely at the level of transcription. Similar observations were made on the regulation of fibrinogen by T3 using rats that received surgical thyroidectomy (TX) as an in vivo model. These results suggest that T3 plays an important role in the process of blood coagulation and inflammation and may contribute to the understanding of the association between thyroid diseases and the misregulation of the inflammatory and clotting profile evident in the circulatory system of these patients.
UR - http://www.scopus.com/inward/record.url?scp=2542501574&partnerID=8YFLogxK
U2 - 10.1210/en.2003-1372
DO - 10.1210/en.2003-1372
M3 - 期刊論文
C2 - 14977860
AN - SCOPUS:2542501574
SN - 0013-7227
VL - 145
SP - 2804
EP - 2814
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -