Arrangement of myofibroblastic and smooth muscle-like cells in superficial peritoneal endometriosis and a possible role of transforming growth factor beta 1 (TGFβ1) in myofibroblastic metaplasia
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Superficial peritoneal endometriotic (pEM) lesions are composed of endometrial glands and stroma, in addition to a third component—myofibroblasts and smooth muscles (SM)-like cells. The latter develops secondary to a metaplasia. In this study, we characterised the third component cells in pEM according to differentiation markers in different micro-compartments. Furthermore, a possible effect of TGFβ1 on myofibroblastic metaplasia in endometriotic epithelial cells was studied.
Seventy-six premenopausal patients were included. Peritoneal biopsies were excised from EM patients (n = 23), unaffected peritoneum (peritoneum from EM patients but without EM components, n = 5/23) and non-EM patients (n = 10). All peritoneal biopsies were immunolabeled for ASMA, calponin, collagen I, desmin, TGFß receptor 1 (R1), R2 and R3 in addition to ultrastructure examination by transmission electron microscopy (TEM) (n = 1). TGFß1 level was measured in peritoneal fluid (PF) (EM, n = 19 and non-EM, n = 13) collected during laparoscopy. Furthermore, TGFß1 effect on myofibroblastic metaplasia was studied in vitro.
At the centre of pEM lesions, calponin immunolabeling outweighs the collagen I while in the periphery the reverse occurs. SM-like cells expressing desmin predominate at the periphery, while ASMA immunolabeling was detectable in all micro-compartments. Both indicate an abundance of myofibroblasts at the centre of pEM lesions and SM-like cells in the periphery. Although activated TGFß1 in PF did not differ between EM and non-EM, it inhibited the cell proliferation of the endometriotic epithelial cells and induced an upregulation in ASMA and collagen IA2 expression as well.
The abundance of the myofibroblasts and SM-like cells points to a myofibroblastic metaplasia in pEM. Both cells are differentially arranged in the different micro-compartments of pEM lesions, with increasing cell maturity towards the periphery of the lesion. Furthermore, TGFß1 may play a role in the myofibroblastic metaplasia of the endometriotic epithelial cells. These findings provide a better insight in the micro-milieu in EM lesions, where most of the disease dynamics occur.
KeywordsPeritoneal endometriosis Myofibroblastic metaplasia TGFβ1 Smooth muscle-like cells
We would like to thank the Ernst Schering Foundation, Germany, and the Humboldt University in Berlin, Germany, for the doctoral scholarships and the FAZIT foundation, Germany, for the travel grant awarded to the first author. We would like to thank Professor Anna Starzinski-Powitz for supplying the cell line.
MG Ibrahim participated in the study design, execution (collected the samples, carrying out the experiments), analysis, manuscript drafting and critical discussion. VC helped in sample collection. ETT, MS, AS and JS did manuscript editing and critical discussion. ETT was the expert of the histopathological staining. JP was the expert for TEM, manuscript editing and critical discussion. MG carried out the real-time PCR and manuscript editing. SM helped with the study design, supervision, manuscript editing and critical discussion.
Compliance with ethical standards
Conflict of interest
The first author was granted scholarships from the Ernst Schering Foundation, the Humboldt University in Berlin and FAZIT foundation in the course of his doctoral work.
All patients included in this study were operated on via laparoscopy at Charité University of Medicine and gave written informed consent. The study was approved by the local research and ethics committee at the Charité University of Medicine, Berlin-Germany (EA4/071/07).
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