HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells

Mol Med Rep. 2016 Jul;14(1):271-6. doi: 10.3892/mmr.2016.5247. Epub 2016 May 11.

Abstract

Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. Epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOX‑A13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)‑induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSA‑induced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction in HKC cells, which were co‑incubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose‑ and time‑dependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSA‑induced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway.

MeSH terms

  • Albumins / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition* / drug effects
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Kidney Tubules / cytology*
  • Receptors, Glucocorticoid / metabolism*
  • Signal Transduction* / drug effects

Substances

  • Albumins
  • Homeodomain Proteins
  • Receptors, Glucocorticoid
  • homeobox protein HOXA13