TY - JOUR
T1 - Endothelin-1 stimulates suppressor of cytokine signaling-3 gene expression in adipocytes
AU - Chang, Hsin Huei
AU - Huang, Yao Ming
AU - Wu, Chi Peng
AU - Tang, Ya Chu
AU - Liu, Chi Wei
AU - Huang, Chun Hsiung
AU - Ho, Low Tone
AU - Wu, Liang Yi
AU - Kuo, Yow Chii
AU - Kao, Yung Hsi
N1 - Funding Information:
This work was supported in part by the National Science Council, Taiwan ( NSC98-2311-B-008-001-MY3 ); Taoyuan Armed Forces General Hospital ( #10003 and #10012 ); Cathay General Hospital and National Central University Joint Research Foundation ( 99CGH-NCU-A1 ); Veteran General Hospital and University System of Taiwan Joint Research Program, and Tsou’s Foundation ( VGHUST98-P3-10 ); and Landseed Hospital and National Central University Joint Research Foundation ( 100LSH-NCU-11 ) to Y.-H.K.
PY - 2012/9/15
Y1 - 2012/9/15
N2 - Endothelin (ET)-1 and suppressor of cytokine signaling (SOCS)-3 were respectively found to regulate energy metabolism and hormone signaling in fat cells. Although ET-1 can also regulate the expression of SOCS-3-stimulating hormones, it is still unknown whether ET-1 regulates SOCS-3 gene expression. This study investigated the pathways involved in ET-1's modulation of SOCS-3 gene expression in 3T3-L1 adipocytes. ET-1 upregulated SOCS-3 mRNA and protein expression in dose- and time-dependent manners. The concentration of ET-1 that increased SOCS-3 mRNA levels by 250-400% was ~100nM with 2-4h of treatment. Treatment with actinomycin D prevented ET-1-stimulated SOCS-3 mRNA expression, suggesting that the effect of ET-1 requires new mRNA synthesis. Pretreatment with the ET type A receptor (ETAR) antagonist, BQ-610, but not the ET type B receptor (ETBR) antagonist, BQ-788, prevented the stimulatory effect of ET-1 on SOCS-3 gene expression. The specific inhibitors of either MEK1 (U-0126 and PD-98059), JAK (AG-490), JNK (SP-600125), or PI3K (LY-294002 and wortmannin) reduced ET-1-increased levels of SOCS-3 mRNA and respectively inhibited ET-1-stimulated activities of MEK1, JAK, JNK, and PI3K. These results imply that the ETAR, ERK, JAK, JNK, and PI3K are functionally necessary for ET-1's stimulation of SOCS-3 gene expression. Moreover, ET-1 was observed to upregulate expressions of SOCS-1, -2, -3, -4, -5, and -6 mRNAs, but not SOCS-7 or cytokine-inducible SH2-containing protein-1 mRNAs. This suggests that ET-1 selectively affects particular types of SOCS family members. Changes in SOCS gene expressions induced by ET-1 may help explain the mechanism by which ET-1 modulates hormone signaling of adipocytes.
AB - Endothelin (ET)-1 and suppressor of cytokine signaling (SOCS)-3 were respectively found to regulate energy metabolism and hormone signaling in fat cells. Although ET-1 can also regulate the expression of SOCS-3-stimulating hormones, it is still unknown whether ET-1 regulates SOCS-3 gene expression. This study investigated the pathways involved in ET-1's modulation of SOCS-3 gene expression in 3T3-L1 adipocytes. ET-1 upregulated SOCS-3 mRNA and protein expression in dose- and time-dependent manners. The concentration of ET-1 that increased SOCS-3 mRNA levels by 250-400% was ~100nM with 2-4h of treatment. Treatment with actinomycin D prevented ET-1-stimulated SOCS-3 mRNA expression, suggesting that the effect of ET-1 requires new mRNA synthesis. Pretreatment with the ET type A receptor (ETAR) antagonist, BQ-610, but not the ET type B receptor (ETBR) antagonist, BQ-788, prevented the stimulatory effect of ET-1 on SOCS-3 gene expression. The specific inhibitors of either MEK1 (U-0126 and PD-98059), JAK (AG-490), JNK (SP-600125), or PI3K (LY-294002 and wortmannin) reduced ET-1-increased levels of SOCS-3 mRNA and respectively inhibited ET-1-stimulated activities of MEK1, JAK, JNK, and PI3K. These results imply that the ETAR, ERK, JAK, JNK, and PI3K are functionally necessary for ET-1's stimulation of SOCS-3 gene expression. Moreover, ET-1 was observed to upregulate expressions of SOCS-1, -2, -3, -4, -5, and -6 mRNAs, but not SOCS-7 or cytokine-inducible SH2-containing protein-1 mRNAs. This suggests that ET-1 selectively affects particular types of SOCS family members. Changes in SOCS gene expressions induced by ET-1 may help explain the mechanism by which ET-1 modulates hormone signaling of adipocytes.
KW - Adipocytes
KW - Endothelin-1
KW - Mitogen-activated protein kinase
KW - Phosphatidylinositol 3-kinase
KW - Suppressor of cytokine signaling
UR - http://www.scopus.com/inward/record.url?scp=84864501838&partnerID=8YFLogxK
U2 - 10.1016/j.ygcen.2012.06.024
DO - 10.1016/j.ygcen.2012.06.024
M3 - 期刊論文
C2 - 22766240
AN - SCOPUS:84864501838
SN - 0016-6480
VL - 178
SP - 450
EP - 458
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
IS - 3
ER -