Silencing of PAQR3 suppresses extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via PI3K/AKT signaling pathway

Eur J Pharmacol. 2018 Aug 5:832:50-55. doi: 10.1016/j.ejphar.2018.05.032. Epub 2018 May 19.

Abstract

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism. Our results demonstrated that HG significantly up-regulated the expression of PAQR3 in human MCs. In addition, knockdown of PAQR3 efficiently suppressed MC proliferation and ECM production in HG-stimulated MCs. Furthermore, knockdown of PAQR3 markedly reversed HG-induced PI3K/AKT activation in MCs. In summary, our present study demonstrated that knockdown of PAQR3 suppressed HG-induced the proliferation and ECM accumulation in human MCs, via inhibiting the PI3K/AKT signaling pathway. Thus, PAQR3 may be a potential therapeutic target for the treatment of diabetic nephropathy.

Keywords: Diabetic nephropathy; Extracellular matrix (ECM); Mesangial cells (MCs); PAQR3.

MeSH terms

  • Dose-Response Relationship, Drug
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Silencing*
  • Glucose / pharmacology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Mesangial Cells / cytology*
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • PAQR3 protein, human
  • Proto-Oncogene Proteins c-akt
  • Glucose