title: Resistin regulates the expression of plasminogen activator inhibitor-1 in 3T3-L1 adipocytes.
abstract: Resistin and plasminogen activator inhibitor-1 (PAI-1) are adipokines, which are secreted from adipocytes. Increased plasma resistin and PAI-1 levels aggravate metabolic syndrome through exacerbation of insulin resistance and induction of chronic inflammation. However, the relationship between resistin and PAI-1 gene expression remains unclear. Previously, we found that resistin regulates lipid metabolism via carbohydrate responsive element-binding protein (ChREBP) during adipocyte maturation (Ikeda et al., 2013) [6]. In this study, to clarify the relationship between expression of resistin and PAI-1, PAI-1 expression in differentiated 3T3-L1 adipocytes was measured after transfection with anti-resistin siRNA. We found that PAI-1 gene expression and secreted PAI-1 protein were significantly decreased by resistin knockdown. Furthermore, phosphorylation of Akt, which can inhibit PAI-1 expression, was accelerated and the activity of protein phosphatase 2A (PP2A) was suppressed in resistin knockdown 3T3-L1 adipocytes. In addition, the expression of glucose transporter type 4, a ChREBP target gene, was reduced and was associated with inhibition of PP2A. The addition of culture medium collected from COS7 cells transfected with a resistin expression plasmid rescued the suppression of PAI-1 expression in resistin knockdown 3T3-L1 adipocytes. Our findings suggest that resistin regulates PAI-1 expression in 3T3-L1 adipocytes via Akt phosphorylation.
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hama
authors.affiliation: Laboratory of Innovative Nanomedicine, Graduate School of Pharmaceutical Sciences, Hokkaido University, Hokkaido 060-0808, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: kogure@mb.kyoto-phu.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D058258:Serpin E2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D051275:Glucose Transporter Type 4; D052243:Resistin; C499623:Retn protein, mouse; D058258:Serpin E2; C511869:Serpine2 protein, mouse; C495693:Slc2a4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2
keywords: Adipocyte; Adipokine; Akt; PAI-1; PP2A; Resistin