PMID- 23559854 OWN - NLM STAT- MEDLINE DCOM- 20130924 LR - 20220409 IS - 1090-0535 (Electronic) IS - 1090-0535 (Linking) VI - 19 DP - 2013 TI - Increased importin 13 activity is associated with the pathogenesis of pterygium. PG - 604-13 AB - PURPOSE: We previously reported that importin 13 (IPO13), a member of the importin-beta 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. FAU - Xu, Ke AU - Xu K AD - Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China. FAU - Tao, Tao AU - Tao T FAU - Jie, Jing AU - Jie J FAU - Lu, Xiaodong AU - Lu X FAU - Li, Xuezhi AU - Li X FAU - Mehmood, Muhammad Aamer AU - Mehmood MA FAU - He, Hui AU - He H FAU - Liu, Zhen AU - Liu Z FAU - Xiao, Xinye AU - Xiao X FAU - Yang, Jie AU - Yang J FAU - Ma, Jian-xing AU - Ma JX FAU - Li, Wei AU - Li W FAU - Zhou, Yueping AU - Zhou Y FAU - Liu, Zuguo AU - Liu Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130320 PL - United States TA - Mol Vis JT - Molecular vision JID - 9605351 RN - 0 (IPO13 protein, human) RN - 0 (Karyopherins) RN - 0 (Keratin-17) RN - 0 (Transcription Factor AP-1) SB - IM MH - Adult MH - Aged MH - Cell Nucleus/metabolism MH - Cell Proliferation MH - Cells, Cultured MH - Epithelial Cells/metabolism/pathology MH - Epithelium/metabolism/pathology MH - Female MH - Gene Expression Regulation MH - Gene Silencing MH - Humans MH - Karyopherins/genetics/*metabolism MH - Keratin-17/genetics/metabolism MH - Male MH - Middle Aged MH - Protein Transport MH - Pterygium/*etiology/genetics/*metabolism/pathology MH - Transcription Factor AP-1/metabolism PMC - PMC3611950 EDAT- 2013/04/06 06:00 MHDA- 2013/09/26 06:00 PMCR- 2013/01/01 CRDT- 2013/04/06 06:00 PHST- 2012/10/08 00:00 [received] PHST- 2013/03/18 00:00 [accepted] PHST- 2013/04/06 06:00 [entrez] PHST- 2013/04/06 06:00 [pubmed] PHST- 2013/09/26 06:00 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - 63 [pii] PST - ppublish SO - Mol Vis. 2013;19:604-13. Epub 2013 Mar 20.