: Corneal endothelial (CE) dysfunction is the main indication for corneal transplantation, an invasive procedure with several limitations. Developing novel strategies to re-activate CE regenerative capacity is, therefore, of fundamental importance. This goal has proved to be challenging as corneal endothelial cells (CEnC) are blocked in the G0/G1 phase of the cell cycle in vivo and, albeit retaining proliferative capacity in vitro, this is further hindered by endothelial-to-mesenchymal transition. Herein we investigated the mechanisms regulating CEnC proliferation in vitro. Comparing the proteome of non-proliferating (in vivo-G0/G1) and proliferating (in vitro-G2/M) rabbit CEnC (rCEnC), 77 proteins, out of 3,328 identified, were differentially expressed in the two groups (p < 0.005). Literature and Gene Ontology analysis revealed β-catenin and transforming growth factor (TGF-β) pathways to be correlated with the identified proteins. Treatment of rCEnC with a β-catenin activator and inhibitor showed that β-catenin activation was necessary during rCEnC proliferation, but not sufficient for its induction. Furthermore, both pro-proliferative activity of basic fibroblast growth factor and anti-proliferative effects of TGF-β were regulated through β-catenin. Overall, these results provide novel insights into the molecular basis underlying the proliferation process that CEnC re-activate in vitro, consolidating the role of β-catenin and TGF-β.

A fine-tuned β-catenin regulation during proliferation of corneal endothelial cells revealed using proteomics analysis / Maurizi, Eleonora; Schiroli, Davide; Zini, Roberta; Limongelli, Anna; Mistò, Raffaela; Macaluso, Claudio; Pellegrini, Graziella. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 10:1(2020), p. 13841. [10.1038/s41598-020-70800-w]

A fine-tuned β-catenin regulation during proliferation of corneal endothelial cells revealed using proteomics analysis

Maurizi, Eleonora;Schiroli, Davide;Macaluso, Claudio;
2020-01-01

Abstract

: Corneal endothelial (CE) dysfunction is the main indication for corneal transplantation, an invasive procedure with several limitations. Developing novel strategies to re-activate CE regenerative capacity is, therefore, of fundamental importance. This goal has proved to be challenging as corneal endothelial cells (CEnC) are blocked in the G0/G1 phase of the cell cycle in vivo and, albeit retaining proliferative capacity in vitro, this is further hindered by endothelial-to-mesenchymal transition. Herein we investigated the mechanisms regulating CEnC proliferation in vitro. Comparing the proteome of non-proliferating (in vivo-G0/G1) and proliferating (in vitro-G2/M) rabbit CEnC (rCEnC), 77 proteins, out of 3,328 identified, were differentially expressed in the two groups (p < 0.005). Literature and Gene Ontology analysis revealed β-catenin and transforming growth factor (TGF-β) pathways to be correlated with the identified proteins. Treatment of rCEnC with a β-catenin activator and inhibitor showed that β-catenin activation was necessary during rCEnC proliferation, but not sufficient for its induction. Furthermore, both pro-proliferative activity of basic fibroblast growth factor and anti-proliferative effects of TGF-β were regulated through β-catenin. Overall, these results provide novel insights into the molecular basis underlying the proliferation process that CEnC re-activate in vitro, consolidating the role of β-catenin and TGF-β.
2020
A fine-tuned β-catenin regulation during proliferation of corneal endothelial cells revealed using proteomics analysis / Maurizi, Eleonora; Schiroli, Davide; Zini, Roberta; Limongelli, Anna; Mistò, Raffaela; Macaluso, Claudio; Pellegrini, Graziella. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 10:1(2020), p. 13841. [10.1038/s41598-020-70800-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2936580
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