Differential expression and function of survivin during the progress of pterygium

Invest Ophthalmol Vis Sci. 2014 Dec 2;55(12):8480-7. doi: 10.1167/iovs.14-15715.

Abstract

Purpose: To investigate the expression pattern and function of survivin in the development of pterygium.

Methods: Primary pterygia at quiescent or advanced clinical stage and normal human conjunctival tissues were used in this study. Pterygium epithelial cells (PECs) were cultured in keratinocyte serum-free defined medium and harvested at different growth stages. Tissue sections and cultured cells were detected with survivin, phosphorylated survivin (Thr43), p63, p57, and p21 on protein, and/or mRNA level. Cell Counting Kit (CCK)-8 assay was performed to measure proliferation status of primary cultured PECs. Small interfering (si) RNA specific for survivin was transfected on PECs at subconfluence stage.

Results: Survivin was highly expressed in all pterygium tissues, but not in normal human conjunctiva, at mRNA and protein levels. It was mainly present in the epithelial cytoplasm of pterygium at quiescent stage, while present in the nucleus of pterygium at advanced stage. Phosphorylated survivin was upregulated in pterygium at advanced stage. Pterygium epithelial cells cultured under subconfluence stage showed higher expression of survivin and p63, but lower expression of p57 and p21, compared with PECs reached confluence. Both total and phosphorylated survivin was mainly expressed in the nuclei of PECs under subconfluence, and there was cytoplasmic translocation of survivin when PECs reached confluence. The knockdown of survivin by siRNA inhibited proliferation of PECs, accompanied by downregulation of p63, and upregulation of p57 and p21.

Conclusions: Higher subcellular expression and phosphorylation of survivin may play roles in the development of pterygium. Survivin could be targeted for the treatment of pterygium.

Keywords: cell proliferation; pterygium; survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Case-Control Studies
  • Cell Nucleus / metabolism
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Conjunctiva / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Inhibitor of Apoptosis Proteins / physiology
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Pterygium / metabolism*
  • Pterygium / physiopathology
  • RNA, Messenger / metabolism
  • Survivin

Substances

  • BIRC5 protein, human
  • CDKN1A protein, human
  • CDKN1C protein, human
  • CKAP4 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p57
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Survivin