title: Inhibition of MicroRNA-21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis.
abstract: BACKGROUND
  Prolonged activation of dermal fibroblasts is the main cause of progressive fibrosis in systemic sclerosis (SSc). It seems that inhibition of apoptosis in SSc fibroblasts deregulates fibrosis. MicroRNA-21 (miR-21) is a pro-fibrotic factor with high expression in lesional areas of SSc skin and fibroblasts.
  
  
  METHODS
  The effects of miR-21 on expression of Bcl-2 and Bax, two apoptotic genes, in dermal fibroblasts of SSc patients were evaluated using real-time polymerase chain reaction and Western blot analysis. Apoptotic cells were detected using flow cytometry and Hoechst 33258 staining assays.
  
  
  RESULTS
  Overexpression of miR-21 using synthetic miR-21 RNA increased expression of Bcl-2, an inhibitor of apoptosis, and decreased the Bax : Bcl-2 expression ratio, a cell fate determinant, in SSc fibroblasts. Antisense inhibition of miR-21 induced a high rate of apoptosis in SSc fibroblasts. We propose that this may be associated with a decrease in Bcl-2 expression and a shift in the Bax : Bcl-2 ratio.
  
  
  CONCLUSIONS
  Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR-21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.
authors.affiliation: Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran.
authors.forename: Saeideh
authors.initials: S
authors.lastname: Jafarinejad-Farsangi
authors.affiliation: Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran. afarazmand@khayam.ut.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Farazmand
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Gharibdoost
authors.affiliation: Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Karimizadeh
authors.affiliation: Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Noorbakhsh
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Habibeh
authors.initials: H
authors.lastname: Faridani
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. jamshida@tums.ac.ir.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Jamshidi
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D020405:Dermis / Q000473:pathology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000494:pharmacology; D061251:Primary Cell Culture; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein