Expression of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs (RECK) Gene and Its Regulation by miR200b in Ovarian Endometriosis

Int J Mol Sci. 2024 Oct 29;25(21):11594. doi: 10.3390/ijms252111594.

Abstract

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis.

Keywords: MMP; RECK; TIMP; adhesions; collagen; endometrial cyst; endometrioma; endometriosis; extracellular matrix; matrix remodeling; mir200.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Endometriosis* / genetics
  • Endometriosis* / metabolism
  • Endometriosis* / pathology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • GPI-Linked Proteins* / genetics
  • GPI-Linked Proteins* / metabolism
  • Gene Expression Regulation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Ovarian Diseases / genetics
  • Ovarian Diseases / metabolism
  • Ovarian Diseases / pathology

Substances

  • MicroRNAs
  • RECK protein, human
  • GPI-Linked Proteins
  • MIRN200 microRNA, human