Journal
CELLS
Volume 11, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/cells11233937
Keywords
caveolin-1; rs1997623; metabolic syndrome; EBF1; AP-2 alpha
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Funding
- Kuwait Foundation for the Advancement of Sciences (KFAS) [RA CB-2021-007]
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The study identified an association between the CAV1 rs1997623 C > A variant and metabolic syndrome, with the A allele generating a transcriptionally active locus that enhances CAV1 expression through the binding of early B-cell factor 1 (EBF1). This is the first demonstration of EBF1's role in regulating CAV1 expression in individuals with the rs1997623 C > A variant through combined in vivo and in vitro experiments.
Caveolin-1 (CAV1) is implicated in the pathophysiology of diabetes and obesity. Previously, we demonstrated an association between the CAV1 rs1997623 C > A variant and metabolic syndrome (MetS). Here, we decipher the functional role of rs1997623 in CAV1 gene regulation. A cohort of 38 patients participated in this study. The quantitative MetS scores (siMS) of the participants were computed. CAV1 transcript and protein expression were tested in subcutaneous adipose tissue using RT-PCR and immunohistochemistry. Chromatin immunoprecipitation assays were performed using primary preadipocytes isolated from individuals with different CAV1 rs1997623 genotypes (AA, AC, and CC). The regulatory region flanking the variant was cloned into a luciferase reporter plasmid and expressed in human preadipocytes. Additional knockdown and overexpression assays were carried out. We show a significant correlation between siMS and CAV1 transcript levels and protein levels in human adipose tissue collected from an Arab cohort. We found that the CAV1 rs1997623 A allele generates a transcriptionally active locus and a new transcription factor binding site for early B-cell factor 1 (EBF1), which enhanced CAV1 expression. Our in vivo and in vitro combined study implicates, for the first time, EBF1 in regulating CAV1 expression in individuals harboring the rs1997623 C > A variant.
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