title: Ultraviolet-A irradiation upregulated urokinase-type plasminogen activator in pterygium fibroblasts through ERK and JNK pathways.
abstract: OBJECTIVE
  Effects of ultraviolet (UV) B on the pterygium and its cells have been studied previously, whereas little is known on the effects of UVA. Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration, and its levels are increased in pterygium. The purpose of our study was to investigate the effects of UVA on the expression of uPA in cultured pterygium fibroblasts.
  
  
  METHODS
  Cultured fibroblasts from early-stage pterygia and normal conjunctiva were irradiated with different dosages of UVA and compared to nonirradiated cells. uPA activities in the medium and uPA mRNA in the cells were measured by casein zymography and RT-PCR, respectively. Total and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), and c-Jun N-terminal kinase (JNK) levels of cells treated with and without UVA were measured by Western blotting. Inhibitors of p38 (SB203580), ERK (UO1026), and JNK (SP600125) were added before the irradiation of UVA to test their effects.
  
  
  RESULTS
  UVA irradiation increased the uPA mRNA levels in pterygium fibroblasts and the uPA activities in cultured medium, which was accompanied with an increase in phosphorylated ERK and JNK. The ERK and JNK inhibitor, but not p38 MAPK inhibitors, significantly decreased the UVA-induced expression of uPA by pterygium fibroblasts. Normal conjunctival fibroblasts were less sensitive to UVA irradiation compared to the pterygium fibroblasts.
  
  
  CONCLUSIONS
  UVA stimulated the production of uPA, a key factor in the modulation of extracellular matrixes, inflammatory processes, and angiogenesis. This may have a role in the development and progression of pterygium.
authors: Department of Ophthalmology, Show Chwan Memorial Hospital, Changhua, Taiwan.
authors: Shih-Chun
authors: SC
authors: Chao
authors: Dan-Ning
authors: DN
authors: Hu
authors: Pei-Yu
authors: PY
authors: Yang
authors: Ching-Yang
authors: CY
authors: Lin
authors: Chan-Wei
authors: CW
authors: Nien
authors: Shun-Fa
authors: SF
authors: Yang
authors: Joan E
authors: JE
authors: Roberts
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000528:radiation effects; D011625:Pterygium / Q000201:enzymology / Q000235:genetics* / Q000532:radiotherapy; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects
chemical_list: D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator