Trisomy 21 impairs PGE2 production in dermal fibroblasts

John O. Marentette, Colin C. Anderson, Kendra M. Prutton, Erin Q. Jennings, Abhishek K. Rauniyar, James J. Galligan, James R. Roede

Research output: Contribution to journalArticlepeer-review

Abstract

The triplication of human chromosome 21 results in Down syndrome (DS), the most common genetic form of intellectual disability. This aneuploid condition also results in an enhanced risk of a spectrum of comorbid conditions, such as leukemia, early onset Alzheimer's disease, and diabetes. Individuals with DS also display an increased incidence of wound healing complications and resistance to solid tumor development. Due to this unique phenotype and the involvement of eicosanoids in key comorbidities like poor healing and tumor development, we hypothesized that cells from DS individuals would display altered eicosanoid production. Using age- and sex-matched dermal fibroblasts we interrogated this hypothesis. Briefly, assessment of over 90 metabolites derived from cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome p450 systems revealed a possible deficiency in the COX system. Basal gene expression and Western blotting experiments showed significantly decreased gene expression of COX1 and 2, and COX2 protein abundance in DS fibroblasts compared to euploid controls. Further, using two different stressors, scratch wound or LPS, we found that DS fibroblasts could not upregulate COX2 abundance and prostaglandin E2 production. Together, these findings show that dermal fibroblasts from DS individuals have a deficient COX2 response, which may contribute to wound healing complications and tumor resistance in DS.

Original languageEnglish (US)
Article number106524
JournalProstaglandins and Other Lipid Mediators
Volume153
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • Arachidonic acid
  • COX2
  • Down syndrome
  • PGE2
  • Prostaglandin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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