title: Profibrotic phenotype of conjunctival fibroblasts from mucous membrane pemphigoid.
abstract: Ocular mucous membrane pemphigoid is an immunobullous disease in which excessive conjunctival fibrosis causes blindness, and the pathogenesis of scarring is incompletely understood. To establish whether profibrotic fibroblasts with an altered phenotype exist in ocular mucous membrane pemphigoid, we compared the functional characteristics of pemphigoid conjunctival fibroblasts to normal conjunctival fibroblasts with respect to cell division; migration; collagen contraction; matrix metalloproteinase, secretion of collagen and chemokines; and myofibroblast differentiation. We found that pemphigoid fibroblasts showed increased cell division (P = 0.01), increased migration in serum-free medium (72 ± 18 migrated cells versus 33 ± 11, P = 0.04), increased collagen contraction in the presence of 10 ng/ml tumor necrosis factor-α, increased collagen type I secretion (P = 0.03), increased secretion of matrix metalloproteinase-3 (P = 0.03), and increased secretion of eotaxin in response to interleukin-13 (P = 0.04). Differences between pemphigoid and normal conjunctival fibroblasts with respect to collagen contraction and MMP secretion in the presence of interleukin-13 were also observed. Together, these findings indicate that pemphigoid conjunctival fibroblasts have a profibrotic phenotype that is maintained in vitro. No differences between pemphigoid fibroblasts obtained from acutely inflamed versus clinically uninflamed conjunctiva were observed. Developing effective antifibrotic therapies will require understanding of the mechanisms that both induce and maintain the profibrotic phenotype.
authors.affiliation: Department of Ocular Biology and Therapeutics, University College London Institute of Ophthalmology, London, UK. v.saw@ucl.ac.uk
authors.forename: Valerie P J
authors.initials: VP
authors.lastname: Saw
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.forename: Ifeoma
authors.initials: I
authors.lastname: Offiah
authors.forename: Grazyna
authors.initials: G
authors.lastname: Galatowicz
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.forename: John K G
authors.initials: JK
authors.lastname: Dart
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Calder
authors.forename: Julie T
authors.initials: JT
authors.lastname: Daniels
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016895:Culture Media, Serum-Free; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D058628:Myofibroblasts / Q000473:pathology; D010390:Pemphigoid, Benign Mucous Membrane / Q000473:pathology*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054413:Chemokine CCL11; D024042:Collagen Type I; D016895:Culture Media, Serum-Free; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3