Increased Expression of Retinol-Binding Protein 4 in Ovarian Endometrioma and Its Possible Role in the Pathogenesis of Endometriosis

Int J Mol Sci. 2021 May 29;22(11):5827. doi: 10.3390/ijms22115827.


Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.

Keywords: adipokine; endometriosis; ovarian endometrioma; retinol-binding protein 4.

MeSH terms

  • Biomarkers
  • Cell Survival
  • Disease Susceptibility*
  • Endometriosis / etiology*
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Female
  • Gene Expression
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Ovary / pathology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / pharmacology
  • Retinol-Binding Proteins, Plasma / genetics*
  • Retinol-Binding Proteins, Plasma / metabolism
  • Retinol-Binding Proteins, Plasma / pharmacology


  • Biomarkers
  • RBP4 protein, human
  • RNA, Small Interfering
  • Recombinant Proteins
  • Retinol-Binding Proteins, Plasma
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9