Regulation and function of collagenous repeat containing sequence of 26-kDa protein gene product "cartonectin".
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Schäffler
Andréas
A
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. andreas.schaeffler@klinik.uni-regensburg.de
Weigert
Johanna
J
Neumeier
Markus
M
Schölmerich
Juergen
J
Buechler
Christa
C
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D054392:Adipokines; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
D054392:Adipokines; D052242:Adiponectin; C499919:Adipoq protein, mouse; C428135:CORS26 protein, mouse; D002839:Chromans; D047492:Peroxisome Proliferator-Activated Receptors; D011506:Proteins; D012333:RNA, Messenger; D052243:Resistin; D045162:Thiazolidinediones; C037112:9-deoxy-delta-9-prostaglandin D2; D000077288:Troglitazone; D015230:Prostaglandin D2; D011345:Fenofibrate