Inhibition by all-trans retinoic acid of collagen degradation mediated by corneal fibroblasts

Kazuhiro Kimura, Hongyan Zhou, Tomoko Orita, Shinya Kobayashi, Tomoyuki Wada, Yoshikuni Nakamura, Teruo Nishida, Koh Hei Sonoda

研究成果: ジャーナルへの寄稿学術誌査読

6 被引用数 (Scopus)

抄録

Background: We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts. Methods: Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IκB-α were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope. Results: All-trans retinoic acid inhibited interleukin-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IκB-α induced by interleukin-1β in these cells. Topical application of all-trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma. Conclusions: All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1β, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration.

本文言語英語
ページ(範囲)502-508
ページ数7
ジャーナルClinical and Experimental Ophthalmology
44
6
DOI
出版ステータス出版済み - 8月 1 2016
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 眼科学

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