Your browser doesn't support javascript.
loading
COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1.
Dankel, Simon N; Grytten, Elise; Bjune, Jan-Inge; Nielsen, Hans Jørgen; Dietrich, Arne; Blüher, Matthias; Sagen, Jørn V; Mellgren, Gunnar.
Affiliation
  • Dankel SN; Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway. simon.dankel@uib.no.
  • Grytten E; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway. simon.dankel@uib.no.
  • Bjune JI; Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Nielsen HJ; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
  • Dietrich A; Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Blüher M; Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
  • Sagen JV; Department of Surgery, Voss Hospital, Bergen Health Trust, Voss, Norway.
  • Mellgren G; Department of Surgery, University of Leipzig, Leipzig, Germany.
Sci Rep ; 10(1): 20164, 2020 11 19.
Article de En | MEDLINE | ID: mdl-33214660
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-ß/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-ß1 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 this mechanism in the regulation of adipose tissue inflammation. In conclusion, we identified the homeobox factor PRRX1 as a novel transcriptional regulator associated with COL6A3 expression, providing new insight into the regulatory mechanisms of altered adipose tissue function in obesity and insulin resistance.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tissu adipeux / Protéines à homéodomaine / Collagène de type VI Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Animals / Humans Langue: En Journal: Sci Rep Année: 2020 Type de document: Article Pays d'affiliation: Norvège

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tissu adipeux / Protéines à homéodomaine / Collagène de type VI Type d'étude: Prognostic_studies / Risk_factors_studies Limites: Animals / Humans Langue: En Journal: Sci Rep Année: 2020 Type de document: Article Pays d'affiliation: Norvège