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

Joseph, D.; Malik, Minnie; Norian, J.M.; Webb, J.; Catherino, William H.

doi:10.1016/j.fertnstert.2007.07.739

Cited by 29 publications

(44 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We evaluated the response of myometrial cells in 3D culture to the cytokine TGF-b3. We have already demonstrated that in 2D cultures the myometrial cells treated with TGF-b3 demonstrate an up-regulation of various ECM genes to levels equivalent to that found in leiomyoma cells (21). As observed in Figure 3, an increased expression of COL1A1 (5.6 AE 0.78), fibronectin …”

Section: Bioactivity Of Cells In 3d Culturessupporting

confidence: 62%

“…We and others have previously demonstrated in 2D cultures that the myometrial cells treated with TGF-b3 demonstrate an up-regulation of various ECM genes to levels comparable to those found in leiomyoma cells (21,32). The 3D myometrial cultures demonstrated a similar up-regulation of RNA transcripts of ECM genes when exposed to cytokine TGF-b3.…”

Section: Discussionmentioning

confidence: 55%

See 1 more Smart Citation

Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Malik

Catherino

2012

Fertility and Sterility

View full text Add to dashboard Cite

Section: Bioactivity Of Cells In 3d Culturessupporting

confidence: 62%

Section: Discussionmentioning

confidence: 55%

Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Malik

Catherino

2012

Fertility and Sterility

View full text Add to dashboard Cite

“…21 The same effect is induced by TGF-b, which stimulates fibronectin mRNA expression in both myometrial and leiomyoma cells. 35 Interestingly, in the present study, the increased fibronectin mRNA expression induced by activin A was prevented by UPA, suggesting that it may also inhibit leiomyoma growth by suppressing activin A fibrotic role in leiomyoma. Uterine leiomyoma is considered as a fibrotic disorder that contains 50% more ECM proteins than the corresponding myometrium.…”

supporting

confidence: 47%

Ulipristal Acetate Modulates the Expression and Functions of Activin A in Leiomyoma Cells

et al. 2014

View full text Add to dashboard Cite

Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age and represents the single most common indication for hysterectomy. A development of new treatments is necessary for a medical management, and in this direction, several hormonal drugs are under investigation. Ulipristal acetate (UPA; a selective progesterone receptor modulator) is considered as one of the most promising because progesterone has a critical role in development and growth of uterine leiomyoma. The effect of steroids is partly mediated by growth factors like activin A which increases extracellular matrix expression contributing to the growth of leiomyoma. The present study aimed to test whether UPA acts on leiomyoma cells affecting expression and functions of activin A system. Cultured myometrial and leiomyoma cells were treated with UPA, and messenger RNA (mRNA) expression levels of activin A (inhibin bA [INHBA] subunits), its binding proteins (follistatin [FST] and FST-related gene), and its receptors (activin receptor-like kinase 4 [ALK4], activin receptor type [ActR] II, and ActRIIB) were evaluated. The effect of UPA on activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells was also studied. Ulipristal acetate decreased INHBA, FST, ActRIIB, and Alk4 mRNA expressions in leiomyoma cultured cells. In addition, UPA was able to block the activin A-induced increase in fibronectin or VEGF-A mRNA expression in myometrial and in leiomyoma cultured cells. The present data show that UPA inhibits activin A expression and functions in leiomyoma cells, and this may represent a possible mechanism of action of the drug on uterine leiomyoma.

show abstract

“…Additionally, TGFβ3 treatment enhanced the expression of fibronectin in both myometrial and leiomyoma cells [40]. Earlier studies demonstrated that collagen type 1 (COL1A1) protein production was higher in untreated leiomyoma than myometrial cells, while Joseph et al demonstrated that elevating TGFβ3 concentration of 0.1 ng/mL to 10 ng/mL resulted in concentration-dependent increase in COL1A1 in both myometrial and leiomyoma cells [41]. Our results from the histopathological analysis of the fucoidantreated (50 mg/kg) group showed a lower expression of fibronectin and α-SMA on ELT-3-LUC-xenografted mice compared to the control group in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The different TGFβ isoforms have their own receptors to regulate signaling pathways [43]. According to previous studies, the TGFβ3 isoform is the major inductor of elevated ECM production and decreased ECM degradation factor production in uterine leiomyoma [41]. Furthermore, uterine leiomyoma has 5-fold higher levels of TGFβ3 mRNA expression than autologous myometrium [11].…”

Section: Discussionmentioning

confidence: 99%

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Chen

Huang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

show abstract

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

Cited by 29 publications

References 0 publications

Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Ulipristal Acetate Modulates the Expression and Functions of Activin A in Leiomyoma Cells

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Contact Info

Product

Resources

About