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L. Motterle, R. Benetti, P. Brun, A. Di Stefano, I. Fregona, A. Leonardi; SMAD Expression in Vernal Keratoconjunctivitis and Conjunctival Fibroblast Cultures. Invest. Ophthalmol. Vis. Sci. 2008;49(13):419.
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© ARVO (1962-2015); The Authors (2016-present)
SMAD proteins modulate the extracellular matrix gene expression during wound healing, inflammation and tissue fibrosis. In this study, we determined SMAD expression in giant papillae of vernal keratoconjunctivitis (VKC) patients and in fibroblast cultures exposed to different mediators that were previously found increased in this disease.
SMAD-2, -3, -7, α-SMA and TGF-β1 were measured in conjunctiva from 6 normal subjects (CT) and 9 VKC patients by immunohistochemistry and western blot (WB). The expression of SMADs, procollagen I (PIP) and TGF-β1 was also determined in conjunctival fibroblast cultures exposed to IL-4, IL-13, TNF-α, TGF-β, eotaxin, histamine, tryptase, elastase and MMP-9.
Immunostaining for SMAD-2, -3, TGF-β and PIP was significantly increased in VKC stroma compared to CT, while SMAD-7 expression was unchanged. However, the WB analysis did not show a significant difference in SMAD expression from homogenized VKC and CT tissues. In conjunctival fibroblasts cultures, SMAD-3 was significantly increased by IFN-γ, TNF-α, IL-13 and IL-4 exposure for 24 hours (p<0.05). SMAD-7 expression was significantly modified only by elastase. TGF-β expression was increased by histamine, IFN-γ, TNF-α, IL-13, IL-4 and eotaxin (p<0.05), while PIP expression was increased by IL-13, IL-4 and reduced by IFN-γ and TNF-α.
The TGF-β/SMAD signaling pathway is over-expressed in VKC tissues and is involved in the fibrillar collagen production.
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