Sunil K Halder1, J Shawn Goodwin, Ayman Al-Hendy. 1. Center for Women’s Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee 37208, USA.
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. CONCLUSION: Vitamin D(3) is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids.
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 humanleiomyoma 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.
Authors: James H Segars; Estella C Parrott; Joan D Nagel; Xiaoxiao Catherine Guo; Xiaohua Gao; Linda S Birnbaum; Vivian W Pinn; Darlene Dixon Journal: Hum Reprod Update Date: 2014-01-08 Impact factor: 15.610
Authors: Erica E Marsh; Geraldine E Ekpo; Eden R Cardozo; Maureen Brocks; Tanaka Dune; Leeber S Cohen Journal: Fertil Steril Date: 2013-03-15 Impact factor: 7.329