COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1.

Scientific Reports
Simon N DankelGunnar Mellgren

Abstract

Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SMAD signaling. Among the identified candidates, the homeobox transcription factor PRRX1 showed a particularly striking co-expression with COL6A3, validated across several different cohorts, including patients with extreme obesity, insulin sensitive and resistant obesity (subcutaneous and omental), after profound fat loss (subcutaneous), and lean controls (subcutaneous). In human and mouse adipose cells, PRRX1 knockdown reduced COL6A3 mRNA and PRRX1 overexpression transactivated a reporter construct with the endogenous human COL6A3 promoter. Stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold specifically after adipogenic induction, whereas TGF-β1 treatment upregulated Col6a3 mRNA also in the preadipocyte state. Interestingly, pro-inflammatory stimulus (i.e., TNF-α treatment) decreased PRRX1-mediated Col6a3 transactivation and mRNA expression, supporting a role for...Continue Reading

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Citations

Jun 11, 2021·The FEBS Journal·Lynn WilliamsJagdeep Nanchahal

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Datasets Mentioned

BETA
E-TABM-862

Methods Mentioned

BETA
biopsies
SGBS
transfection
biopsy
FCS
PCR

Software Mentioned

QuikChange Primer Design
PASW Statistics

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