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H. Lee, S.-I. Choi, T.-I. Kim, E. Kim; The Different Expression Pattern of Alpha 3 Integrin and Its Implication Between Granular Dystrophy Type Ii (Avellino Dystrophy) and Normal Corneal Fibroblast. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5869.
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© ARVO (1962-2015); The Authors (2016-present)
Because alpha3 beta1 integrin is a well known cellular receptor for bigh3 protein, we investigate the difference of expression of integrin alpha 3 beta1 in cultured corneal fibroblast between Granular dystrophy type II (Avellino dystrophy) and normal patients. And the role of alpha 3 integrin in bigh3 protein production and its interaction with beta1 integrin were also investigated.
Corneal fibroblasts isolated from homozygote patient and disease free cornea after penetrating Keratoplasty were cultured with DMEM+10% FBS. Baseline and TGF-beta1 stimulated expression of alpha 3 and beta 1 integrin were compared between both fibroblasts through western immunoblot and FACS assay. The signal transduction for alpha 3 beta 1 integrin was investigated and compared between GD type II corneal fibroblast and normal corneal fibroblast. Also, transcription activity of AP-1 and FOX were determined in both fibroblasts.
The basal expression and transcription activity of alpha 3 integrin was higher in homozygote GD type II fibroblast. With TGF-b1 treatment, the alpha 3 integrin expression was increased in both cell types. However, the basal beta 1 integrin expression did not show the difference. Beta 1 integrin expression was down-regulated by TGF-beta1 treatment in normal corneal fibroblast. However, beta1 integrin was up-regulated by TGF-b1 treatment in GD type II fibroblast. Also, those TGF-b1 induced beta1 integrin expression was neutralized by transfection of alpha 3 integrin dominant negative plasmid.
The basal and TGF-beta stimulated expression of alpha 3 integrin were different between both cell types. The elevated activity of alpha 3 integrin in GD type II fibroblast was related with the transcription activity of AP-1 and may affect the expression of beta 1 integrin and TGF-beta 1 induced cellular uptake of bigh3 protein. The difference of integrin regulation between normal and GD type II cornea may provide an important pathophysiologic clue for development and progression of GD type II.
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