title: 1,25-Dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells.
abstract: BACKGROUND
  Uterine leiomyomas (fibroids) are the most common benign estrogen-dependent tumors of premenopausal women. TGF-β3 up-regulates the synthesis of many of extracellular matrix proteins that are associated with tissue fibrosis.
  
  
  OBJECTIVE
  To examine the effect of 1,25-dihydroxyvitamin D(3) (vitamin D(3)) on TGF-β3-induced fibrosis-related protein expression in immortalized human uterine leiomyoma (HuLM) cells.
  
  
  METHODS
  HuLM cells were treated with TGF-β3 with or without vitamin D(3). Western blot analyses were employed to test the effect of vitamin D(3) on TGF-β3-induced protein expression of collagen type 1, fibronectin, and plasminogen activator inhibitor-1 proteins. Western blots as well as immunofluorescence analyses were used to verify the effect of vitamin D(3) on TGF-β3-induced Smad activation involved in extracellular matrix protein synthesis and deposition, which ultimately lead to tissue fibrosis.
  
  
  RESULTS
  We observed that TGF-β3 induced fibronectin and collagen type 1 protein expression in HuLM cells, and that effect was suppressed by vitamin D(3). TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitamin D(3). Additionally, TGF-β3 induced phosphorylation of Smad2 as well as nuclear translocation of Smad2 and Smad3 in HuLM cells, whereas vitamin D significantly reduced all these TGF-β3-mediated effects. Therefore, our results suggest that vitamin D(3) has consistently reduced TGF-β3 effects that are involved in the process of fibrosis in human leiomyoma cells.
  
  
  CONCLUSIONS
  Vitamin D(3) is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids.
authors.affiliation: Center for Women’s Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee 37208, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Halder
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Goodwin
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
mesh_terms: D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D051785:Smad Proteins; D053782:Transforming Growth Factor beta3; D002117:Calcitriol