title: Lovastatin Reduces Stemness via Epigenetic Reprograming ofBMP2andGATA2in Human Endometrium and Endometriosis.
abstract: OBJECTIVE
  The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such asBMP2,GATA2andRUNX2as well as eMSCs markers.
  
  
  METHODS
  In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin,BMP2,RUNX2andGATA2expressions were measured by real-time polymerase chain reaction (PCR). To determine involvement of DNA methylation inBMP2andGATA2gene regulations of eMSCs, we used quantitative Methylation Specific PCR (qMSP) for evaluation of theBMP2promoter status and differentially methylated region ofGATA2exon 4.
  
  
  RESULTS
  In the present study, treatment with lovastatin increased expression ofBMP2andRUNX2and inducedBMP2promoter demethylation. We also demonstrated that lovastatin treatment down-regulatedGATA2expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group.
  
  
  CONCLUSIONS
  These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Taghizadeh
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Noruzinia
keywords: Endometriosis; Epigenetics; Lovastatin; Stemness