Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor β-3

Joseph, D.; Malik, Minnie; Nurudeen, S.K.; Catherino, William H.

doi:10.1016/j.fertnstert.2009.01.081

Cited by 79 publications

(43 citation statements)

References 62 publications

(73 reference statements)

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“…We (16) and others (17) have demonstrated elevated expression of fibronectin in leiomyoma compared with myometrium, and have demonstrated that TGF- β 3 stimulates fibronectin expression in myometrial and leiomyoma cells. In prior studies, treatment of myometrial cells with ATRA decreased fibronectin expression in a dose-dependent matter in 2D cell culture (22).…”

Section: Resultsmentioning

confidence: 81%

“…We previously demonstrated that TGF- β 3 was expressed at a higher concentration in leiomyoma tissue than myometrium and in leiomyoma cells when compared with myometrial cells in 2D cell cultures (15, 16, 36). However, it was not clear whether TGF- β 3 would remain elevated in the presence of ECM.…”

Section: Resultsmentioning

confidence: 98%

“…Expression of type I collagen in leiomyoma specimens is known to be greater than in myometrium (16, 38, 39). Furthermore, TGF- β 3 exerts a dose-dependent stimulatory effect in myometrial and leiomyoma cells on COL1A1 mRNA and protein production (16).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, TGF- β 3 exerts a dose-dependent stimulatory effect in myometrial and leiomyoma cells on COL1A1 mRNA and protein production (16). We also showed that COL1A1 expression was inhibited by ATRA treatment (22).…”

Section: Resultsmentioning

confidence: 99%

“…The characteristic of elevated TGF- β expression seen in fibrotic disease has also been identified in uterine leiomyomas (15–17). TGF- β 3 increased production of proteoglycans and collagens, which leads to the fibrotic phenotype of leiomyomata (15, 16, 18, 19). TGF- β 3 exerts its effect through the mothers against decanpentaplegic (Smad) signaling cascade that transfers signal from the membrane to the nucleus and effects gene expression (20).…”

mentioning

confidence: 99%

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Liarozole inhibits transforming growth factor-β3–mediated extracellular matrix formation in human three-dimensional leiomyoma cultures

Levy

Malik

Britten

et al. 2014

Fertility and Sterility

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Objective To investigate the impact of liarozole on transforming growth factor-β3 (TGF-β3) expression, TGF-β3 controlled profibrotic cytokines, and extracellular matrix formation in a three-dimensional (3D) leiomyoma model system. Design Molecular and immunohistochemical analysis in a cell line evaluated in a three-dimensional culture. Setting Laboratory study. Patient(s) None. Intervention(s) Treatment of leiomyoma and myometrial cells with liarozole and TGF-β3 in a three-dimensional culture system. Main Outcome Measure(s) Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blotting to assess fold gene and protein expression of TGF-β3 and TGF-β3 regulated fibrotic cytokines: collagen 1A1 (COL1A1), fibronectin, and versican before and after treatment with liarozole, and confirmatory immunohistochemical stains of treated three-dimensional cultures. Result(s) Both TGF-β3 gene and protein expression were elevated in leiomyoma cells compared with myometrium in two-dimensional and 3D cultures. Treatment with liarozole decreased TGF-β3 gene and protein expression. Extracellular matrix components versican, COL1A1, and fibronectin were also decreased by liarozole treatment in 3D cultures. Treatment of 3D cultures with TGF-β3 increased gene expression and protein production of COL1A1, fibronectin, and versican. Conclusion(s) Liarozole decreased TGF-β3 and TGF-β3–mediated extracellular matrix expression in a 3D uterine leiomyoma culture system.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Liarozole inhibits transforming growth factor-β3–mediated extracellular matrix formation in human three-dimensional leiomyoma cultures

Levy

Malik

Britten

et al. 2014

Fertility and Sterility

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Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids

Islam

Afrin

Singh

et al. 2021

Clinical & Translational Med

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Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

Islam

Akhtar

Ciavattini

et al. 2014

Molecular Nutrition Food Res

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Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70–80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids.

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Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor β-3

Cited by 79 publications

References 62 publications

Liarozole inhibits transforming growth factor-β3–mediated extracellular matrix formation in human three-dimensional leiomyoma cultures

Liarozole inhibits transforming growth factor-β3–mediated extracellular matrix formation in human three-dimensional leiomyoma cultures

Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

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