Moxifloxacin modifies corneal fibroblast-to-myofibroblast differentiation

作者：Chen T C; Chang S W^*; Wang T Y

来源：British Journal of Pharmacology, 2013, 168(6): 1341-1354.

DOI：10.1111/bph.12015

• MOX
• HCFs
• TGFBR1
• TGFBR2
• fibroblast-to-myofibroblast differentiation
• -SMA filament formation
• Smad2 phosphorylation

Background and Purpose Fibroblast-to-myofibroblast differentiation is associated with scarring, an important issue in corneal surgery. Moxifloxacin (MOX), commonly applied to prevent post-operative infection, would benefit more if it modifies fibroblast-to-myofibroblast differentiation other than antimicrobial activity. Our purpose was to explore whether MOX has anti-fibrotic effect in human corneal fibroblasts (HCFs). Experimental Approach HCFs were incubated in MOX-containing medium concurrently with TGF-1 (co-treatment), before (pretreatment) or after (post-treatment) adding TGF-1. HCF contractility was evaluated with a type I collagen gel contraction assay. Expression of -smooth muscle actin (-SMA), Smad2, phospho-Smad2-Ser467, Smad4 and Smad7 was determined by immunoblotting. Formation of -SMA-positive filaments and distribution of active Smad2 were observed under confocal microscopy. Expression of TGF- receptor types I (TGFBR1) and II (TGFBR2) was assessed with flow cytometry. Key Results MOX did not affect gel contractility or -SMA filament formation in HCFs without TGF-1 stimulation. MOX did, however, retard HCF-containing gel contractility and -SMA filament formation following TGF-1 stimulation in the pretreatment and co-treatment groups but not in the post-treatment group. MOX blocked the expression of Smad2, phospho-Smad2-Ser467 and TGFBR1 under TGF-1 incubation. Additionally, MOX enhanced Smad7 expression in TGF-1-incubated HCFs, but did not interfere with TGF--triggered Smad2 nuclear translocation or Smad4 expression. Conclusions and Implications MOX inhibited TGF--induced fibroblast-to-myofibroblast differentiation via blocking TGFBR1 and enhancing Smad7 expression. MOX should be used before or during surgery to achieve these effects. These results suggest a de novo mechanism by which MOX participates in corneal wound healing.

• 出版日期2013-3