title: Increased importin 13 activity is associated with the pathogenesis of pterygium.
abstract: OBJECTIVE
  We previously reported that importin 13 (IPO13), a member of the importin-β family of nuclear import proteins, regulates nuclear import of the glucocorticoid receptor in airway epithelial cells, IPO13 serves as a potential marker for corneal epithelial progenitor cells, and IPO13 is associated with corneal cell proliferation. Here we investigated the role of IPO13 in the pathogenesis of pterygium and the underlying mechanism including interaction with other cell proliferation-related factors: keratin 17 (K17), a lesional protein and a member of the type I keratins, and c-Jun, a protein of the activator protein-1 complex.
  
  
  METHODS
  Tissue samples were collected from primary pterygia, recurrent pterygia, and normal conjunctiva to perform the following experiments: immunohistochemical measurement of IPO13 and K17. Pterygium epithelial cells (PECs) were cultured in keratinocyte serum-free defined medium to examine the expression of IPO13 and K17. Lentivirus-mediated silencing and overexpression IPO13 testing was conducted, and K17 alternation was evaluated with western blot and immunostaining. In addition, the translocation of c-Jun (a K17 regulator) was further examined after IPO13 was silenced.
  
  
  RESULTS
  IPO13 activity was significantly increased in the basal layer of the epithelium of the pterygium. In cultured PECs, overexpression or knockdown of the IPO13 gene increased or decreased PEC proliferation, respectively. IPO13 was colocalized with K17 in the epithelium of the pterygium, and overexpression or knockdown of the IPO13 gene induced upregulation or downregulation of K17 expression in PECs, respectively. In addition, silencing of the IPO13 gene blocked nuclear translocation of c-Jun.
  
  
  CONCLUSIONS
  We provided novel evidence that IPO13 may contribute to the pathogenesis of pterygium via modulation of K17 and c-Jun.
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.forename: Jing
authors.initials: J
authors.lastname: Jie
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lu
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Li
authors.forename: Muhammad Aamer
authors.initials: MA
authors.lastname: Mehmood
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinye
authors.initials: X
authors.lastname: Xiao
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D053537:Keratin-17 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D011625:Pterygium / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C527880:IPO13 protein, human; D028884:Karyopherins; D053537:Keratin-17; D018808:Transcription Factor AP-1
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