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목적 : Statin has been reported to have a beneficial effect on glaucoma. In this study, we intended to investigate the effect of statins on Transforming growth factor beta 2 (TGF-β2)-mediated expression of extracellular matrix (ECM) proteins in human astrocytes of optic nerve head (ONH) lamina cribrosa (LC).
방법 : Astrocytes cultured from LC of human donor ONH were treated with recombinant TGF-β2 at concentrations of 1, 5 and 10 ng/mL for 24 hours and were subjected to western blotting. To test activation of Smad2/3, astrocytes were pretreated with Simvastatin or Lovastatin of 5ug/ml for 1hr and then treated with TGF-β2 for 1hr. Cell nuclear were counterstained with 4,6-diamidino-2-phenylindole,dihydrochloride. Confocal image were used to fluorescence microscope and Zeiss ZEN imaging software
결과 : TGF-β2 induced the expression of ECM related proteins in human ONH astrocytes.
Both Simvastatin and Lovastatin effectively inhibited TGF-β2-mediated expression of connective tissue growth factor (CTGF), collagen I, fibronectin and plasminogen activator inhibitor (PAI)-1. Both Simvastatin and Lovastatin attenuated the Smad2/3 nuclear localization by TGF-β2 confirming that statins inhibit Smad2/3 activation by TGF-β2.
결론 : We demonstrated anti-fibrotic effect of statins in human astrocytes of ONH and identified TGF-β2 as a mediator of statin action, which may support beneficial effect of statins on glaucomatous axonal damage induced by ECM remodeling. In order to translate these findings into the therapeutic application, in vivo analysis on the effect of statins on ECM remodeling is need to be performed.
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