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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.
This article was published in the following journal.
Name: Journal of cellular and molecular medicine
Recent studies have demonstrated that IGF-1 modulates the pluripotent differentiation of dental pulp stem cells (DPSCs). Although mTOR pathway activation has been showed as responsible for IGF-1 induc...
Profilin 1 (PFN1) protein plays key roles in neuronal growth and differentiation, membrane trafficking, and regulation of the actin cytoskeleton. Four natural variants of PFN1 were described as relate...
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An adaptor protein, consisting of seven WD REPEATS along its length, that functions as a component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 and MTORC2 COMPLEX. It interacts directly with MTOR to enhance its kinase activity and stabilizes the MTOR-RPTOR PROTEIN interaction in nutrient-poor conditions, favoring RPTOR inhibition of MTOR activity.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.
Ophthalmology is the branch of medicine that is devoted to the study and treatment of eye diseases. As well as mild visual defects correctable by lenses, ophthalmology is concerned with glaucoma, uveitis and other serious conditions affecting the eye, ...
Track and monitor developments in stem cell research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry. BioPort...
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...