title: Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction of resident fibroblasts to the presence of ectopic endometrium.
abstract: BACKGROUND
  In this study, we characterized the fibromuscular (FM) tissue, typical of deeply infiltrating endometriosis, investigated which cells are responsible for the FM reaction and evaluated whether transforming growth factor-beta (TGF-beta) signaling is involved in this process.
  
  
  METHODS
  FM differentiation and TGF-beta signaling were assessed in deeply infiltrating endometriosis lesions (n = 20) and a nude mouse model of endometriosis 1, 2, 3 and 4 weeks post-transplantation. The FM reaction was evaluated by immunohistochemistry using different markers of FM and smooth muscle cell differentiation (vimentin, desmin, alpha-smooth muscle actin, smooth muscle myosin heavy chain). TGF-beta signaling was assessed by immunostaining for its receptors and phosphorylated Smad.
  
  
  RESULTS
  Deeply infiltrating endometriosis lesions contain myofibroblast-like cells that express multiple markers of FM differentiation. Expression of TGF-beta receptors and phospho-Smad was more pronounced in the endometrial component of the lesions than in the FM component. In the nude mouse model, alpha-smooth muscle actin expression was observed in murine fibroblasts surrounding the lesion, but not in human endometrial stroma.
  
  
  CONCLUSIONS
  FM differentiation in deeply infiltrating endometriosis is the result of a reaction of the local environment to the presence of ectopic endometrium. It shares characteristics with pathological wound healing, but cannot be explained by TGF-beta signaling alone.
authors: Research Institute GROW, University of Maastricht/University Hospital Maastricht, Maastricht, The Netherlands. kimvankaam@yahoo.com
authors: K J A F
authors: KJ
authors: van Kaam
authors: J P
authors: JP
authors: Schouten
authors: A W
authors: AW
authors: Nap
authors: G A J
authors: GA
authors: Dunselman
authors: P G
authors: PG
authors: Groothuis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002828:Choristoma / Q000473:pathology; D004715:Endometriosis / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009130:Muscle, Smooth / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2