Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

Ciarmela, Pasquapina; Islam, Soriful; Reis, Fernando M.; Gray, Peter C.; Bloise, Enrrico; Petraglia, Felice; Vale, Wylie; Castellucci, Mario

doi:10.1093/humupd/dmr031

Cited by 207 publications

(212 citation statements)

References 189 publications

(336 reference statements)

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…There is significant evidence in the literature supporting a progesterone-and TGFB-mediated role in the proliferation of uterine fibroids (reviewed by Rein et al (1995), Ciarmela et al (2011) and Kim & Sefton (2012)). TGFBR2 gene expression was decreased in fibroidderived A K C C SMC relative to myometrium.…”

Section: Discussionmentioning

confidence: 99%

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Holdsworth-Carson¹,

Zaitseva²,

Girling³

et al. 2014

Reproduction

View full text Add to dashboard Cite

Uterine fibroids are a prevalent gynaecological condition in reproductive-aged women and are the commonest reason for hysterectomy. The cellular composition of clonal fibroids are heterogeneous, with phenotypically dissimilar cells that include smooth muscle cells (SMC), vascular SMC (VSMC) and fibroblasts. The aim of our study was to investigate genes that are commonly differentially expressed between fibroid and myometrial whole tissues in phenotypically different sub-populations of cells isolated from fibroid and myometrium. Genes to be investigated by fluorescence-activated cell sorting, quantitative real-time PCR and immunocytochemistry include transforming growth factor b (TGFB) and retinoic acid (RA) signalling families and steroid hormone receptors. We hypothesised that each cell population isolated from fibroid and myometrium would differ in the expression of fibroid-associated genes. We demonstrated that phenotypically different cellular constituents of uterine fibroids differentially express cellular RA-binding protein 2 (CRABP2), progesterone receptor B (PRB) and TGFB receptor 2 mRNA in fibroid-derived cells of VSMC and SMC phenotype. CRABP2 mRNA was also differentially expressed in fibroblasts and VSMC sub-populations from within clonal fibroid tumours. We conclude that differential regulation of RA, TGFB and PR pathway transcription occurs in fibroid-associated SMC and -fibroblasts and that investigation of paracrine interactions between different cell types within the fibroid microenvironment provides an important new paradigm for understanding the pathophysiology of this common disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Holdsworth-Carson¹,

Zaitseva²,

Girling³

et al. 2014

Reproduction

View full text Add to dashboard Cite

show abstract

“…Poprzez działanie autokrynne i parakrynne wpływają na prawidłowe funkcjonowanie błony śluzowej macicy przez stymulację podziałów mitotycznych oraz różnicowanie komórek. Ponadto zaangażowane są w prawidłowe procesy interakcji endometrium-trofoblast, wczesne etapy utrzymania ciąży, złuszczanie tkanki przy braku implantacji, jak również w funkcjonalne procesy regeneracyjne endometrium (9,21,24). Niewłaściwa aktywność tych substancji powodowana zaburzeniami ekspresji kodujących je genów prowadzić może do istotnej deregulacji procesów wzrostu i apoptozy komórek.…”

Section: Artykuł Przeglądowy Reviewunclassified

“…EGF ma istotny wpływ na proliferację, różnicowanie, żywot-ność oraz funkcjonalną aktywność różnego typu komó-rek zarówno w żywym organizmie, jak i warunkach in vitro (9). Ponadto reguluje procesy homeostazy tkankowej.…”

Section: Nabłonkowy Czynnik Wzrostu (Epidermal Growth Factor Egf)unclassified

Relevant aspects of the influence of chosen growth factors on the activity of the female reproductive system

Woźna¹,

Rybska²,

Swierczewska³

et al. 2017

Medycyna Weterynaryjna

View full text Add to dashboard Cite

*) Projekt został sfinansowany ze środków Narodowego Centrum Nauki przyznanych na podstawie decyzji DEC-2013/09/N/NZ5/0183. Woźna M., Rybska M., Świerczewska M., Jaśkowski J. M.Relevant aspects of the influence of chosen growth factors on the activity of the female reproductive system Summary The endometrium of the uterus is a highly dynamic structure in terms of its changes during the various stages of the sexual cycle. These changes are the result of cyclical fluctuations in the concentrations of steroid hormones and local factors of an auto -and paracrine -nature. This condition indicates that the causes of degenerative processes of the uterus must be sought not only in disorders of the hormonal profile and bacterial infections but also disorders at the molecular level. Factors that may play a key role in the formation and development of various pathologies of the female reproductive system include growth factors and their receptors (growth factors -GFs). Discussing these growth factors in the work may provide useful molecular markers that identify pathological conditions of the endometrium. Subject to expression in the endometrium, they are involved in the regulation of cell proliferation, migration and secretion of the glandular epithelium, they also regulate physiological and pathological angiogenesis, revealing strong pro-inflammatory effects. In this research, the authors present an overview of current scientific reports indicating that changes in the expression of studied factors, and thus disturbances in their effects, may constitute one of the causes of pathogenesis within the uterus in many animal species.

show abstract

“…Лейомиома матки относится к наиболее рас-пространенным гинекологическим заболевани-ям, частота ее встречаемости среди пациенток репродуктивного возраста, по данным раз-ных авторов, составляет от 40 до 80 % [1,2]. Лейомиома развивается предположительно в результате трансформации клеток миометрия и состоит из гладкомышечных клеток и боль-шого количества внеклеточного матрикса [3].…”

Section: Introductionunclassified

Molecular mechanisms of regulation of uterine leiomyoma growth

et al. 2017

View full text Add to dashboard Cite

Background: to elucidate the molecular mechanisms, regulating growth and proliferation of leiomyoma cells, the estimation of the activity of PR-A and PR-B isoforms of progesterone receptor and PI3K/Akt and MAPК kinases, participating in signal transduction from sex steroids and growth factors, has the special interest. Aim of the work: to investigate the character of the expression of mRNAs of PR-A and PR-B isoforms of progesterone receptor in leiomyomas of different size and different intensity of cellular proliferation, and to elucidate the relationship between the PR-A and PR-B synthesis and activation of PI3K/Akt and MAPК signaling pathways in tumour tissue. Materials and Methods. The examination of the PR-A, PR-B, Akt, PTEN, ERK and Ki67 mRNAs expression in normal myometrium and leiomyoma tissues of 29 women with uterine leiomyoma was performed using RP-PCR. Results. It was found that in general the leiomyoma tissue was characterized by the high level of PR-A, PTEN and ERK mRNAs expression comparing to the miometrium. Distinctive characteristic of the small leiomyomas and leiomyomas with low proliferative activity was the highest synthesis of PR-A isoform of progesterone receptor. In large leiomyomas and in proliferating Ki67+ leiomymas the significant increase of ERK mRNA expression was seen. Conclusion. Activation of the PR-A isoform of progesterone receptor and MAPK/ERK signaling pathway associated with the inhibition of PI3K/Akt signaling due to high synthesis of PTEN plays the important role in mechanisms, regulating leiomyoma growth.

show abstract

Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications

Abstract: Growth factors play an important role in the mechanisms involved in myometrial patho-physiology.

Cited by 207 publications

References 189 publications

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium

Relevant aspects of the influence of chosen growth factors on the activity of the female reproductive system

Molecular mechanisms of regulation of uterine leiomyoma growth

Contact Info

Product

Resources

About