title: Endothelin-1 stimulates suppressor of cytokine signaling-3 gene expression in adipocytes.
abstract: 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 (ET(A)R) antagonist, BQ-610, but not the ET type B receptor (ET(B)R) 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 ET(A)R, 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.
authors: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan.
authors: Hsin-Huei
authors: HH
authors: Chang
authors: Yao-Ming
authors: YM
authors: Huang
authors: Chi-Peng
authors: CP
authors: Wu
authors: Ya-Chu
authors: YC
authors: Tang
authors: Chi-Wei
authors: CW
authors: Liu
authors: Chun-Hsiung
authors: CH
authors: Huang
authors: Low-Tone
authors: LT
authors: Ho
authors: Liang-Yi
authors: LY
authors: Wu
authors: Yow-Chii
authors: YC
authors: Kuo
authors: Yung-Hsi
authors: YH
authors: Kao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019332:Endothelin-1 / Q000494:pharmacology*; D051379:Mice; D016133:Polymerase Chain Reaction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D050826:Suppressor of Cytokine Signaling Proteins