Regulation and Function of Collagenous Repeat Containing Sequence of 26‐kDa Protein Gene Product “Cartonectin”

Abstract

Collagenous repeat containing sequence of 26-kDa protein (CORS-26) was identified as a new gene transcript expressed in cartilage with unknown function. It was the aim of this study to investigate expression, regulation, and function of CORS-26 in adipocytes. CORS-26 mRNA and protein expression was studied by reverse transcriptase-polymerase chain reaction, Western blot analysis, and quantitative real-time polymerase chain reaction. Transcriptional regulation was studied by electrophoretic mobility shift assay and luciferase reporter gene assay. The adipocytic secretion of adiponectin and resistin was measured by enzyme-linked immunosorbent assay. CORS-26 mRNA is absent in 3T3-L1 preadipocytes and adipocytes after 48 hours of differentiation. CORS-26 mRNA was induced from Day 4 to Day 9 of adipocyte differentiation. CORS-26 protein was induced in mature adipocytes. Peroxisome proliferator-activated receptor (PPAR) gamma (but not PPARalpha) in nuclear extracts prepared from adipocytes was shown to bind specifically to a putative peroxisome proliferator response element-one-half-site located at -641/-596 bp. Increasing doses of the ligands troglitazone (1, 10, 20 microM) and fenofibrate (50, 100, 200 microM) but not 15-deoxy-prostaglandin (J(2)) (0.5, 1.0, 2.5 microM) resulted in a significant reduction of both promoter activity and the amount of mRNA expression. Recombinant CORS-26 significantly stimulated the adipocytic secretion of adiponectin and resistin in a dose-dependent manner. The mRNA and protein expression profile puts CORS-26 in the adipocytokine family. Cartonectin is negatively regulated by exogenous, but not endogenous, PPARgamma ligands. Because CORS-26 up-regulates adipokine secretion, it might be involved in metabolic and immunologic pathways.