title: Induction of TIMP-1 and HSP47 synthesis in primary keloid fibroblasts by exogenous nitric oxide.
abstract: BACKGROUND
  The excessive accumulation of extracellular matrix is a hallmark of many fibrotic diseases, including the hypertrophic scar and keloid. Recent reports from this research team had shown that exogenous nitric oxide (NO) participates in the keloid formation; however, its role on the synthesis of fibrotic factor (TGF-beta1, TIMP-1 and HSP47) in the keloid fibroblasts (KF) remained unclear.
  
  
  OBJECTIVE
  In this study, to better define the potential effect of exogenous NO on the expression of fibrotic factors in KF, the enhancing effect of exogenous NO, released from a NO donor, on the synthesis of fibrotic factors in KF was investigated.
  
  
  METHODS
  The seven primary KF cultures were set up to measure the effect of exogenous NO on enhancing the expression of fibrotic factor.
  
  
  RESULTS
  Elevation of cellular cGMP levels was observed to be induced by NO or blocked by the hydrolysis activity of phosphodiesterase (PDE) by the PDE inhibitor. The elevated levels of cellular cGMP were noted to enhance the expression of TIMP-1 and HSP47 in KF. Exogenous NO was found to significantly accelerate the production of TIMP-1 and HSP47 in the seven primary KFs with a corresponding increase in the production of TGF-beta1.
  
  
  CONCLUSIONS
  The results have led to a conclusion, that is: the excess collagen formations in the keloid lesion may be attributed to the NO/cGMP signal pathway by initiating a rapid increase in the expression of TGF-beta1, TIMP-1 and HSP47 in the KF cells.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. d8702008@tmu.edu.tw <d8702008@tmu.edu.tw>
authors.forename: Yi-Chiang
authors.initials: YC
authors.lastname: Hsu
authors.forename: Leng-Fang
authors.initials: LF
authors.lastname: Wang
authors.forename: Yie W
authors.initials: YW
authors.lastname: Chien
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D050958:HSP47 Heat-Shock Proteins; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011994:Recombinant Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D006152:Cyclic GMP