title: Junctional basement membrane anomalies of skin and mucosa in lipoid proteinosis (hyalinosis cutis et mucosae).
abstract: BACKGROUND
  Excessive basement membrane (BM) deposition in skin and mucosa is characteristic for lipoid proteinosis (LP; hyalinosis cutis et mucosae), an inherited disease caused by extracellular matrix protein 1 (ECM1) mutations. According to ultrastructure there are striking differences between junctional and microvascular BM.
  
  
  OBJECTIVE
  Distinct analysis of the junctional zone in epidermis and oral mucosa, contrasting concentric BM arrays in the microvasculature; evaluation of impact on epithelial histogenesis and differentiation, and specifically on adhesion structures to BM (hemidesmosomes).
  
  
  METHODS
  LP-epithelia were analyzed for alterations in differentiation, BM composition and texture, and hemidesmosomal components by indirect immunofluorescence (IIF), electron microscopy (EM), and immunoelectron microscopy (ImEM).
  
  
  RESULTS
  Most striking was the irregular deposition of collagen IV and VII, BM-laminin, and laminin-5 at the junctional zone, accompanied by lamellate or punctuated structures below BM (IIF), whereas integrin alpha6beta4 and bullous pemphigoid antigen-1 and -2 (BPAG-1/-2) were regularly aligned. Also integrins alpha2beta1 and alpha3beta1 remained restricted to the epidermal basal layer, while the tissue-specific differentiation markers keratin K1/10 (mucosa, additionally K4/13) appeared delayed indicating mild hyperplasia, further confirmed by focal K6/16 expression. Ultrastructure (EM) disclosed abundance of extended basal cell protrusions and junctional aberrations like exfoliating excessive BM material. Hemidesmosomes were complete, but ImEM indicated weakened interactions between their components (BPAG-1, -2, and HD1). Confirming IIF, collagen IV and VII, and laminin-5 appeared extensively scattered, the latter two probably remaining associated.
  
  
  CONCLUSIONS
  Subtle defects in anchorage assembly, spanning the entire BM zone, apparently compromise epithelial-matrix adhesion, which may provoke (mechanical stress-induced) erroneous BM repair.
authors.affiliation: German Cancer Research Center, Division Genetics of Skin Cancer, Heidelberg, Germany.
authors.forename: Nicolae
authors.initials: N
authors.lastname: Mirancea
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hausser
authors.forename: Dieter
authors.initials: D
authors.lastname: Metze
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stark
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.forename: Dirk
authors.initials: D
authors.lastname: Breitkreutz
mesh_terms: D000328:Adult; D001485:Basement Membrane / Q000473:pathology / Q000648:ultrastructure; D015415:Biomarkers; D001706:Biopsy; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D004817:Epidermis / Q000473:pathology* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D009061:Mouth Mucosa / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D015415:Biomarkers