title: Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.
abstract: OBJECTIVE
  To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.
  
  
  METHODS
  Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alphaSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels.
  
  
  RESULTS
  Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed alphaSMA and increased types I and IV collagens. VKC-FBs, and in particular all alphaSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change alphaSMA expression, while alphaSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein.
  
  
  CONCLUSIONS
  The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC.
authors.affiliation: CIR Laboratory of Ophthalmology, University Campus Bio-medico, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lambiase
authors.forename: Barbara
authors.initials: B
authors.lastname: Stampachiacchiere
authors.forename: Roberto
authors.initials: R
authors.lastname: Sgrulletta
authors.forename: Eduardo Maria
authors.initials: EM
authors.lastname: Normando
authors.forename: Sergio
authors.initials: S
authors.lastname: Bonini
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonini
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D003233:Conjunctivitis, Allergic / Q000473:pathology* / Q000503:physiopathology*; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000199:Actins; D024042:Collagen Type I; D024141:Collagen Type IV; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020780:Matrix Metalloproteinase 9