1,25-Dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells

J Clin Endocrinol Metab. 2011 Apr;96(4):E754-62. doi: 10.1210/jc.2010-2131. Epub 2011 Feb 2.


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.

Conclusion: Vitamin D(3) is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / pharmacology*
  • Calcitriol / therapeutic use
  • Cell Line, Transformed
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Fibronectins / metabolism
  • Fibrosis / chemically induced
  • Fibrosis / genetics
  • Fibrosis / prevention & control
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Leiomyoma / drug therapy
  • Leiomyoma / genetics
  • Leiomyoma / metabolism
  • Leiomyoma / pathology*
  • Phosphorylation / drug effects
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Protein Binding / drug effects
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta3 / antagonists & inhibitors
  • Transforming Growth Factor beta3 / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*


  • Fibronectins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Smad Proteins
  • Transforming Growth Factor beta3
  • Calcitriol