title: Rosiglitazone drives cavin-2/SDPR expression in adipocytes in a CEBPα-dependent manner.
abstract: Caveolae are abundant adipocyte surface domains involved in insulin signaling, membrane trafficking and lipid homeostasis. Transcriptional control mechanisms for caveolins and cavins, the building blocks of caveolae, are thus arguably important for adipocyte biology and studies in this area may give insight into insulin resistance and diabetes. Here we addressed the hypothesis that one of the less characterized caveolar components, cavin-2 (SDPR), is controlled by CCAAT/Enhancer Binding Protein (CEBPα) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG). Using human mRNA expression data we found that SDPR correlated with PPARG in several tissues. This was also observed during differentiation of 3T3-L1 fibroblasts into adipocytes. Treatment of 3T3-L1-derived adipocytes with the PPARγ-activator Rosiglitazone increased SDPR and CEBPα expression at both the mRNA and protein levels. Silencing of CEBPα antagonized these effects. Further, adenoviral expression of PPARγ/CEBPα or Rosiglitazone-treatment increased SDPR expression in primary rat adipocytes. The myocardin family coactivator MKL1 was recently shown to regulate SDPR expression in human coronary artery smooth muscle cells. However, we found that actin depolymerization, known to inhibit MKL1 and MKL2, was without effect on SDPR mRNA levels in adipocytes, even though overexpression of MKL1 and MKL2 had the capacity to increase caveolins and cavins and to repress PPARγ/CEBPα. Altogether, this work demonstrates that CEBPα expression and PPARγ-activity promote SDPR transcription and further supports the emerging notion that PPARγ/CEBPα and MKL1/MKL2 are antagonistic in adipocytes.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Hansson
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rippe
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kotowska
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wasserstrom
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Säll
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Göransson
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swärd
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Karin G
authors.initials: KG
authors.lastname: Stenkula
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D028044:Phosphate-Binding Proteins; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C112303:CAVIN2 protein, human; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D002352:Carrier Proteins; C431575:MRTFA protein, human; C478036:MRTFB protein, human; D047495:PPAR gamma; D028044:Phosphate-Binding Proteins; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D000077154:Rosiglitazone