title: Upregulated stromal cell-derived factor 1 (SDF-1) expression and its interaction with CXCR4 contribute to the pathogenesis of severe pterygia.
abstract: OBJECTIVE
  Stromal cell-derived factor 1 (SDF-1) and its interaction with chemokine receptor 4 (CXCR4) have been noted for participating in the wound healing process, and may paradoxically develop hypertrophic scarring. With viewing pterygia as a product of exaggerated wound formation, we evaluated the effects of SDF-1 and CXCR4 on determining the severity of pterygia.
  
  
  METHODS
  Human pterygial fibroblasts were cultured from excised tissues. Then, expression levels of SDF-1 and CXCR4 were assessed at both the mRNA and protein levels and analyzed with respect to the severity (grade T1 to T3) of pterygia. Expression patterns of SDF-1 and CXCR4 in pterygium tissues were evaluated by immunohistochemistry. Additionally, to investigate the SDF-1-induced myofibroblast transformation of pterygial fibroblasts, the correlation between SDF-1 and α-smooth muscle actin (α-SMA) expression levels was evaluated. Furthermore, α-SMA levels in pterygial fibroblasts were determined before and after knockdown of SDF-1 and blockade of CXCR4 by AMD3100.
  
  
  RESULTS
  Stromal cell-derived factor 1 and CXCR4 were expressed in identical areas in severe pterygium tissues (grade T3) and CXCR4-immunopositive cells were concentrated at perivascular regions. Stromal cell-derived factor 1 levels in cultured pterygial fibroblasts correlated positively with the severity of pterygia. Stromal cell-derived factor 1 levels had a significant, positive correlation with α-SMA levels in pterygial fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF-1/CXCR4 signaling in severe pterygia significantly reduced α-SMA levels.
  
  
  CONCLUSIONS
  Stromal cell-derived factor 1 expression is upregulated in severe pterygia, and SDF-1 and CXCR4 interaction may contribute to the myofibroblast transformation, which can be possibly restored through the downregulation of the SDF-1/CXCR4 axis.
authors.affiliation: Department of Ophthalmology, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Kyoung Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae Chan
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001596:Benzylamines; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D000080027:Cyclams; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects; D011446:Prospective Studies; D011625:Pterygium / Q000209:etiology*; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: CXCR4; SDF-1; alpha-SMA; myofibroblast