title: Possible involvement of inflammatory/reparative processes in the development of uterine fibroids.
abstract: Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020, Ancona, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Protic
authors.affiliation: Department of Medical Biotechnology, University of Siena, 53100, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020, Ancona, Italy.|Biotechnology and Microbiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, 6205, Bangladesh.
authors.forename: Md Soriful
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Medical Biotechnology, University of Siena, 53100, Siena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Occhini
authors.affiliation: Department of Clinical Science, Polytechnic University of Marche, 60131, Ancona, Italy.
authors.forename: Stefano Raffaele
authors.initials: SR
authors.lastname: Giannubilo
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Catherino
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020, Ancona, Italy.|Center of Obesity, Polytechnic University of Marche - United Hospitals, Ancona, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.affiliation: Department of Molecular and Developmental Medicine, Obstetrics, and Gynecology, University of Siena, 53100, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.affiliation: Department of Clinical Science, Polytechnic University of Marche, 60131, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciavattini
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020, Ancona, Italy. m.castellucci@univpm.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Castellucci
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, M5S 3E2, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, Polytechnic University of Marche, via Tronto 10/a, 60020, Ancona, Italy. p.ciarmela@univpm.it.|Department of Information Engineering, Polytechnic University of Marche, Ancona, Italy. p.ciarmela@univpm.it.
authors.forename: Pasquapina
authors.initials: P
authors.lastname: Ciarmela
mesh_terms: D000199:Actins / Q000378:metabolism; D028341:Activins / Q000276:immunology; D018952:Antigens, CD34 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D018230:Leiomyoma, Epithelioid / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D009215:Myometrium / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014594:Uterine Neoplasms / Q000276:immunology / Q000473:pathology*; D014599:Uterus / Q000473:pathology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D003893:Desmin; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; D003094:Collagen
keywords: Activin A; CD34; Cellular leiomyoma; ECM; Inflammation; Myofibroblast; Myometrium; TNF-α; Usual leiomyoma