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Sci Rep ; 8(1): 13140, 2018 09 03.
Article in English | MEDLINE | ID: mdl-30177722

ABSTRACT

Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-ß dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-ß dependent cell differentiation.


Subject(s)
Conjunctiva/metabolism , Cornea/metabolism , Dry Eye Syndromes/genetics , Gelsolin/genetics , Re-Epithelialization/genetics , Actins/genetics , Actins/metabolism , Animals , Cell Differentiation , Cell Proliferation , Conjunctiva/pathology , Cornea/pathology , Dry Eye Syndromes/blood , Dry Eye Syndromes/pathology , Epithelial Cells/cytology , Epithelial Cells/metabolism , Eyelids/cytology , Eyelids/metabolism , Female , Gelsolin/blood , Gene Expression Regulation , Humans , Lacrimal Apparatus/metabolism , Lacrimal Apparatus/pathology , Male , Mice , Myofibroblasts/cytology , Nasolacrimal Duct/cytology , Nasolacrimal Duct/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Wound Healing/genetics
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