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Endothelin‐1 stimulates resistin gene expression (LB756)
Author(s) -
Liu ChiWei,
Tang YaChu,
Chang HsinHuei,
Juan ChiChang,
Kuo YowChii,
Kao ChungCheng,
Huang YaoMing,
Kao YungHsi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb756
Subject(s) - wortmannin , resistin , endocrinology , medicine , ly294002 , phosphorylation , protein kinase b , signal transduction , kinase , downregulation and upregulation , stat3 , chemistry , biology , microbiology and biotechnology , insulin resistance , gene , insulin , adiponectin , biochemistry
Resistin and endothelin (ET)‐1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET‐1 to act on resistin gene expression is still unknown. Using 3T3‐L1 adipocytes, we investigated the signaling pathways involved in ET‐1‐stimulated resistin gene expression. The upregulation of resistin mRNA expression by ET‐1 depends on concentration and timing. The concentration of ET‐1 that increased resistin mRNA levels by 100‐250% was approximately 100 nM for a range of 0.25~12 h of treatment. Treatment with actinomycin D blocked ET‐1‐increased resistin mRNA levels, suggesting that the effect of ET‐1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type‐A receptor (ETAR), such as BQ610, but not with the ET type‐B receptor (ETBR) antagonist BQ788, blocked ET‐1‐increased the levels of resistin mRNA and phosphorylated levels of downstream signaling molecules such as ERK1/2, JNKs, AKT, and STAT3. Moreover, pretreatment of specific inhibitors of either ERK1/2 (U0126 and PD98059), JNKs (SP600125), PI3K/AKT (LY294002 and Wortmannin), or JAK2/STAT3 (AG490) prevented ET‐1‐increased levels of resistin mRNA and reduced the ET‐1‐stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist SB203580 did not alter the effect of ET‐1. These results imply that ETAR, ERK1/2, JNKs, AKT, and JAK2, but not ETBR or p38, are necessary for the ET‐1 stimulation of resistin gene expression. In vivo observations that ET‐1 increased resistin mRNA and protein levels in subcutaneous and epididymal adipose tissues support the in vitro findings.