Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0081544
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dc.titleHevin plays a pivotal role in corneal wound healing
dc.contributor.authorChaurasia S.S.
dc.contributor.authorPerera P.R.
dc.contributor.authorPoh R.
dc.contributor.authorLim R.R.
dc.contributor.authorWong T.T.
dc.contributor.authorMehta J.S.
dc.date.accessioned2020-03-26T06:45:14Z
dc.date.available2020-03-26T06:45:14Z
dc.date.issued2013
dc.identifier.citationChaurasia S.S., Perera P.R., Poh R., Lim R.R., Wong T.T., Mehta J.S. (2013). Hevin plays a pivotal role in corneal wound healing. PLoS ONE 8 (11) : e81544. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0081544
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165965
dc.description.abstractBackground: Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin -/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. Methodology/Principal Findings: Wild type (WT) and hevin-/- mice were divided into three groups at 4 time points-1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. Conclusions/Significance: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin -/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing. Copyright: © 2013 Chaurasia et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectcollagen type 1
dc.subjectcollagen type 4
dc.subjecthevin
dc.subjectmatrix metalloproteinase
dc.subjectscleroprotein
dc.subjectunclassified drug
dc.subjectvasculotropin
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectarticle
dc.subjectchronic inflammation
dc.subjectcontrolled study
dc.subjectcornea cell
dc.subjectcornea injury
dc.subjectcornea neovascularization
dc.subjectcornea stroma
dc.subjectcorneal haze
dc.subjectfibrosis
dc.subjectkeratectomy
dc.subjectkeratitis
dc.subjectmouse
dc.subjectmyofibroblast
dc.subjectnonhuman
dc.subjectophthalmic excimer laser
dc.subjectprotein expression
dc.subjectupregulation
dc.subjectwound healing
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCalcium-Binding Proteins
dc.subjectCornea
dc.subjectCorneal Stroma
dc.subjectExtracellular Matrix Proteins
dc.subjectFibroblasts
dc.subjectFibrosis
dc.subjectGene Expression
dc.subjectIn Situ Nick-End Labeling
dc.subjectInflammation
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectNeovascularization, Pathologic
dc.subjectWound Healing
dc.typeArticle
dc.contributor.departmentDEPT OF CHEMISTRY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pone.0081544
dc.description.sourcetitlePLoS ONE
dc.description.volume8
dc.description.issue11
dc.description.pagee81544
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