1. PFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells
- Author
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Carla Giordano, Valentina Failla, Salvatore Cillino, Laura Tomasello, Antonina Coppola, Giuseppe Pizzolanti, Maria Pitrone, Tomasello L., Coppola A., Pitrone M., Failla V., Cillino S., Pizzolanti G., and Giordano C.
- Subjects
0301 basic medicine ,limbal stem cell ,Apoptosis ,integrin-β1 ,Settore MED/13 - Endocrinologia ,Profilins ,0302 clinical medicine ,signalling ,Cells, Cultured ,Corneal epithelium ,Integrin beta1 ,TOR Serine-Threonine Kinases ,Epithelium, Corneal ,Cell Differentiation ,Cell biology ,medicine.anatomical_structure ,mTOR pathway ,030220 oncology & carcinogenesis ,Molecular Medicine ,Original Article ,Stem cell ,Homeobox protein NANOG ,integrin‐β1 ,regenerative medicine ,Biology ,Limbus Corneae ,Corneal limbus ,03 medical and health sciences ,stem cells ,medicine ,Humans ,profilin ,Fibroblast ,limbal stem cells ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Wound Healing ,Settore MED/30 - Malattie Apparato Visivo ,Cell Biology ,Original Articles ,Fibroblasts ,eye diseases ,epithelial differentiation ,030104 developmental biology ,Gene Expression Regulation ,Eye disorder ,sense organs ,corneal regeneration ,Wound healing ,Biomarkers - Abstract
Ex vivo limbal stem cell transplantation is the main therapeutic approach to address a complete and functional re‐epithelialization in corneal blindness, the second most common eye disorder. Although important key points were defined, the molecular mechanisms involved in the epithelial phenotype determination are unclear. Our previous studies have demonstrated the pluripotency and immune‐modulatory of fibroblast limbal stem cells (f‐LSCs), isolated from the corneal limbus. We defined a proteomic profile especially enriched in wound healing and cytoskeleton‐remodelling proteins, including Profilin‐1 (PFN1). In this study we postulate that pfn‐1 knock down promotes epithelial lineage by inhibiting the integrin‐β1(CD29)/mTOR pathway and subsequent NANOG down‐expression. We showed that it is possible modulate pfn1 expression levels by treating f‐LSCs with Resveratrol (RSV), a natural compound: pfn1 decline is accompanied with up‐regulation of the specific differentiation epithelial genes pax6 (paired‐box 6), sox17 (sex determining region Y‐box 17) and ΔNp63‐α (p63 splice variant), consistent with drop‐down of the principle stem gene levels. These results contribute to understand the molecular biology of corneal epithelium development and suggest that pfn1 is a potential molecular target for the treatment of corneal blindness based on epithelial cell dysfunction.
- Published
- 2019