Ulipristal acetate decreases active TGF-β3 and its canonical signaling in uterine leiomyoma via two novel mechanisms

Lewis, Terrence D.; Malik, Minnie; Britten, Joy; Parikh, Toral; Cox, J.; Catherino, William H.

doi:10.1016/j.fertnstert.2018.12.026

Cited by 29 publications

(24 citation statements)

References 56 publications

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“…As we discussed above, different isoforms of TGF-β may play a crucial role in uterine fibroid development. Studies that used anti-uterine fibroid agents cause the attenuation of this pathway by reducing TGF-β3 signal and protein expression, resulting in a reduction in TGF-β canonical signaling [103]. Therefore, canonical Wnt pathway has been suggested to be a potential therapeutic target for the treatment of uterine fibroids [104].…”

Section: Treatment Of Uterine Fibroidmentioning

confidence: 99%

Herbal Medicine in Uterine Fibroid

Li¹,

Huang²,

Ho³

et al. 2021

Fibroids

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Uterine fibroids, also known as uterine leiomyoma is the most common benign tumor of the uterus found in women of reproductive age. Uterine fibroids are the cause of major quality-of-life issues for approximately 25% of all women who suffer from clinically significant symptoms of uterine fibroid. Despite the prevalence of fibroid, currently, there are no effective treatment options for fibroid. The lack of understanding of the etiology of fibroid contributes to the scarcity of medical therapies available. Sex steroid hormones, dysregulation of cell signaling pathways, miRNA expression, and cytogenetic abnormalities may all implicate in fibroid etiology. Several herbal medicines have been used as anti-inflammation and antitumor agents. All of them have a common capability to inhibit expression of pro-inflammatory cytokines, proliferative genes, and pro-angiogenetic genes. Exploring herbal medicines as remedies lighten the hope of treatment. In the current review article, we discuss signal transduction pathways activated herbal medicines. We also address the possibility of using herbal medicines for uterine fibroid treatment.

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Section: Treatment Of Uterine Fibroidmentioning

confidence: 99%

Herbal Medicine in Uterine Fibroid

Li¹,

Huang²,

Ho³

et al. 2021

Fibroids

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“…This may ultimately cause non-effective decrease in uterine size after hormonal medication, (2) while most of the other studies examined in vitro effect of hormonal therapy on the individual components of ECM, we investigated the effect of GnRHa on the highly accumulated ECM and collagen fibers with resultant visible fibrosis in biopsy specimens. Recently, ulipristal acetate (GnRHa antagonist) shows promising effect on inhibiting leiomyoma fibrosis via decreasing TGF-β3 and its canonical signaling pathway as well as by limiting cell proliferation and ECM remodeling [36,63,64].…”

Section: Plos Onementioning

confidence: 99%

“…All these results indicate that GnRHa has a significant potential in reducing symptoms, fibroid size and risk of bleeding during surgery. Ulipristal acetate has been reported to attenuate cascade of fibrosis by reducing TGF-β3 mRNA and protein expression with consequent reduction of leiomyoma fibrosis [36]. However, pattern of fibrosis in different uterine leiomyomas and myometrium and changes in the accumulation of fibrosis after hormonal treatment is unclear.…”

Section: Introductionmentioning

confidence: 99%

Expression profiles of E/P receptors and fibrosis in GnRHa-treated and -untreated women with different uterine leiomyomas

et al. 2020

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Differential expressions of estrogen/progesterone receptors (ER/PR) and individual component of extracellular matrices derived from fibroid are reported. Information on the pattern of change in ER/PR expression and amount of tissue fibrosis after hormonal treatment is unclear. We investigated pattern of change in ER/PR expression and percentage of tissue fibrosis in different uterine leiomyomas after gonadotropin-releasing hormone agonist (GnRHa) treatment. Biopsy specimens from fibroids and adjacent myometria were collected after surgery from women with submucosal myoma (SMM, n = 18), intramural myoma (IMM, n = 16) and subserosal myoma (SSM, n = 17). A proportion of women in each group of fibroid underwent treatment with GnRHa for a variable period of 3–6 months. Tissue expression of ER and PR was analyzed by immunohistochemistry. In vitro cell proliferation effect of GnRHa on human umbilical vein endothelial cells (HUVECs) was examined. Distribution of tissue fibrosis was examined by Masson’s trichrome staining with computer-captured image analysis of fibrosis derived from different types of fibroid. PR content was significantly higher than ER in tissues derived from GnRHa-untreated women with SMM and SSM (p = 0.04 for both). Comparing to untreated group, GnRHa-treatment significantly decreased either ER or PR expression in different fibroids. Exogenous treatment with GnRHa dose-dependently decreased proliferation of HUVECs. No significant difference was observed in the percentage of fibrosis in tissues collected from GnRHa-treated and -untreated women with fibroids. The distribution of fibrosis in myoma/myometria and occurrence of fibrosis in perivascular area showed an increasing trend with higher age of the women and with larger size of fibroids. Our findings suggest that despite estrogen dependency, higher PR content in GnRHa-untreated group may indicate a potential role of progesterone in leiomyoma growth. Although GnRHa therapy may shrink fibroids and reduce risk of bleeding during surgery, the occurrence of diffuse tissue fibrosis may impair effective reduction of fibroid size after hormonal treatment.

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“…To better understand this mechanism, Lewis at al. (5) analyzed the effect of UPA on TGF-b3 canonical and noncanonical signaling pathways in UFs. They proved that UPA affects ECM protein production through the attenuation of transcription and translation of TGF-b3.…”

mentioning

confidence: 99%