A fine-tuned β-catenin regulation during proliferation of corneal endothelial cells revealed using proteomics analysis
Maurizi E, Schiroli D, Zini R, Limongelli A, Mistò R, Macaluso C, Pellegrini G.
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.
Sci Rep. 2020 Aug 14;10(1):13841.
DOI: 10.1038/s41598-020-70800-w
Search
Tag
Recent Posts
- Newcastle pharmacy experts work with Italian biotech lab to provide access to sight-saving treatment across England
- Holostem Terapie Avanzate begins its transition to a Foundation
- Transgenic Epidermal Cultures for Junctional Epidermolysis Bullosa — 5-Year Outcomes
- Gene therapy for butterfly children: 5-year follow-up published in the New England Journal of Medicine
- Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa