1,25-Dihydroxyvitamin D3 reduces TGF-β3-induced fibrosis-related gene expression in human uterine leiomyoma cells

Sunil K. Halder, J. Shawn Goodwin, Ayman Al-Hendy

Research output: Contribution to journalArticle

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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 D3 (vitamin D3) 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 D3 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 D3 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 D3. TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitaminD3. 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 D3 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.

Original languageEnglish (US)
Pages (from-to)E754-E762
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number4
DOIs
StatePublished - Apr 1 2011

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Calcitriol
Cholecalciferol
Leiomyoma
Gene expression
Fibrosis
Gene Expression
Extracellular Matrix Proteins
Plasminogen Activator Inhibitor 1
Collagen Type I
Proteins
Fibronectins
Tissue
Phosphorylation
Replication Protein C
Western Blotting
Vitamin D
Tumors
Estrogens
Chemical activation
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

1,25-Dihydroxyvitamin D3 reduces TGF-β3-induced fibrosis-related gene expression in human uterine leiomyoma cells. / Halder, Sunil K.; Goodwin, J. Shawn; Al-Hendy, Ayman.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 4, 01.04.2011, p. E754-E762.

Research output: Contribution to journalArticle

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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 D3 (vitamin D3) 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 D3 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 D3 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 D3. TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitaminD3. 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 D3 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.",
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