Open AccessPFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells
Author(s) -
Tomasello Laura,
Coppola Antonina,
Pitrone Maria,
Failla Valentina,
Cillino Salvatore,
Pizzolanti Giuseppe,
Giordano Carla
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14438
Subject(s) - stem cell , microbiology and biotechnology , biology , homeobox protein nanog , corneal epithelium , fibroblast , pax6 , cancer research , wound healing , pi3k/akt/mtor pathway , cornea , induced pluripotent stem cell , immunology , embryonic stem cell , epithelium , signal transduction , genetics , cell culture , gene , transcription factor , neuroscience
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.