RESUMEN
PURPOSE: Transforming growth factor-β-induced protein (TGFBIp) is highly expressed in the cornea, and mutant TGFBIp induces corneal diseases. However, the function of TGFBIp in cornea epithelium is not fully investigated. Here, we tested the importance of TGFBIp in regulation of gene expression and corneal epithelial cell (CEC) activity. MATERIALS AND METHODS: The effect of TGFBIp on CEC activity was analyzed by cell migration, adhesion, proliferation and wound healing assay. Analysis of gene expression was examined by western blot and quantitative reverse transcription PCR. RESULTS: The results demonstrated that TGFBIp increased adhesion, migration, proliferation, and wound healing of CECs. Analysis of gene expression presented that TGFBIp-stimulated CECs exhibited increased expression of mucin family genes, such as MUC1, -4, -5AC, and -16. Furthermore, TGFBIp treatment increased the expression of MUC1, -4, -5AC, -7, and -16 in conjunctival epithelial cells. TGFBIp also increased the activity of intracellular signaling molecules ERK and AKT in CECs. Using pharmacologic inhibitors of ERK and AKT, we showed that the expression of mucin genes by TGFBIp is mediated by the activation of ERK and AKT signaling. CONCLUSION: Our findings demonstrate that the locally generated TGFBIp in the cornea may contribute to wound healing of CECs by enhancing the migration, adhesion, and proliferation of CECs. In addition, our results suggest that TGFBIp has a protective effect on ocular surfaces by inducing the expression of mucin genes in corneal and conjunctival epithelial cells. These data suggest that TGFBIp is a useful therapeutic target for patients with corneal wounds.
Asunto(s)
Humanos , Western Blotting , Movimiento Celular , Córnea , Enfermedades de la Córnea , Células Epiteliales , Epitelio , Expresión Génica , Regulación de la Expresión Génica , Mucinas , Reacción en Cadena de la Polimerasa , Transcripción Reversa , Cicatrización de Heridas , Heridas y LesionesRESUMEN
Granular corneal dystrophy is a rare autosomal dominant genetic disease in clinic.Due to the TGFBI mutation on the 5q31 chromosome,the TGFBIp abnormally aggregates in the Bowman layer and the matrix layer and metabolic disorders,patients' bilateral cornea arise opacity,making visual acuity Progressive impairment.At present,there are at least 66 TGFBI mutations,at least 10 of which are related to granular corneal dystrophy,due to variation in genotype and the difference between homozygous and heterozygous,the patients' phenotype shows a significant difference.Along with the improvement of people's cognition,and the application of laser scanning confocal microscope and the gene diagnosis,More and more patients get the correct diagnosis,Current treatment methods mainly include corneal transplantation and laser ablation,patients are not satisfied because of the postoperative recurrence and aggravated.Due to the establishment of granular corneal dystrophy animal model,lithium and gene therapy will show a good application prospects.