UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts

Alexios J Aletras1, Ioannis Trilivas2, Maria-Elpida Christopoulou3

  • 1Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26 504, Patras, Greece. aletras@chemistry.upatras.gr.

BMC Ophthalmology
|December 20, 2018
PubMed
Abstract

Insights

UVB exposure reduces proteasome subunit PSMB5 expression in pterygium fibroblasts via the Nrf2/ARE pathway, potentially involving src kinases. This may explain lower PSMB5 levels in pterygium tissue.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Cell Biology

Background:

  • Pterygium involves corneal epithelial overgrowth, inflammation, and extracellular matrix accumulation, with chronic UV exposure as a key factor.
  • The proteasome, particularly the β5 (PSMB5) subunit, plays a role in protein degradation, with its expression often regulated by the Nrf2-ARE pathway.
  • This study focuses on PSMB5 expression and activity in pterygium and the impact of UVB irradiation on pterygium fibroblasts.

Purpose of the Study:

  • To investigate the expression levels of the proteasome subunit PSMB5 in pterygium.
  • To determine the effect of ultraviolet B (UVB) irradiation on PSMB5 expression and proteasome activity in pterygium fibroblasts.
  • To elucidate the role of the Nrf2-ARE pathway and src kinases in UVB-induced changes in PSMB5 expression.

Main Methods:

  • Specimens of normal conjunctiva and pterygium were collected for fibroblast isolation.
  • Expression of PSMB5 and Nrf2 was analyzed using RT-PCR and western blotting.
  • Cell survival was assessed via MTT assay, and proteasome chymotrypsin-like activity was measured by fluorometry.

Main Results:

  • PSMB5 expression was significantly lower in pterygium tissues compared to normal conjunctiva.
  • UVB irradiation suppressed PSMB5 and Nrf2 expression in pterygium fibroblasts in a dose-dependent manner.
  • Src kinase inhibition partially restored PSMB5 expression after UVB exposure, suggesting its involvement.

Conclusions:

  • UVB exposure down-regulates Nrf2/ARE-mediated PSMB5 gene expression in pterygium fibroblasts, with potential involvement of src kinases.
  • This UVB-induced down-regulation of PSMB5 may contribute to the reduced PSMB5 levels observed in pterygium compared to normal conjunctiva.

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