Key role of transcription factors network in proliferative vitreoretinal diseases development.
| Title: | Key role of transcription factors network in proliferative vitreoretinal diseases development. |
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| Authors: | Duveau C; Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.; Department of Ophthalmology, Brussels University Hospital - Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.; Raiss El Harrak Y; Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.; Department of Ophthalmology, Brussels University Hospital - Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.; Datlibagi A; Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.; Department of Ophthalmology, Brussels University Hospital - Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.; Ophthalmology Department, HUmani - CHU Charleroi-Chimay, Charleroi, Belgium.; Ophthalmology Department, CHU Helora, Mons, Belgium.; Perret J; Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium.; Willermain F; Department of Ophthalmology, CHU St Pierre and Brugmann, Brussels, Belgium.; I.R.I.B.H.M. J. E. Dumont, Université Libre de Bruxelles, Brussels, Belgium.; Delporte C; Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, Brussels, Belgium. christine.delporte@ulb.be.; Motulsky E; Department of Ophthalmology, Brussels University Hospital - Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. |
| Source: | Cell & bioscience [Cell Biosci] 2026 May 08. Date of Electronic Publication: 2026 May 08. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101561195 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2045-3701 (Print) Linking ISSN: 20453701 NLM ISO Abbreviation: Cell Biosci |
| Imprint Name(s): | Original Publication: London : BioMed Central, 2011- |
| Abstract: | Proliferative vitreoretinal diseases (PVDs) encompass severe ocular disorders such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and epiretinal membranes (ERM), characterized by the formation of fibrovascular membranes that often lead to retinal detachment and vision loss. A central mechanism driving these conditions is the epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, orchestrated by a network of transcription factors (TFs). Among these, zinc finger E-box binding homeobox 1 (ZEB1) emerges as a pivotal regulator by repressing epithelial markers like E-cadherin and inducing mesenchymal markers such as N-cadherin and vimentin, thereby promoting cell migration and fibrotic membrane formation. nuclear factor of activated T cells 5 (NFAT5) contributes to this process by mediating osmotic stress responses and upregulating inflammatory cytokines, which further act upon EMT and fibrosis. activator protein 1 (AP-1) and hypoxia inducible factor 1 subunit alpha (HIF-1α) participate in driving inflammation, extracellular matrix (ECM) remodeling, and angiogenesis. While HIF-1α triggers vascular endothelial growth factor (VEGF) expression under hypoxic conditions, AP-1 modulates matrix metalloproteinases (MMPs) essential for ECM degradation and remodeling. Additional TFs, including Kruppel-like factor 4 (KLF4) and microphthalmia-associated transcription factor (MITF), are vital in maintaining RPE cell identity. Their downregulation under pathological conditions disrupts epithelial integrity and predisposes cells to undergo EMT. Moreover, β-catenin, through its role in the wingless-related integration site (Wnt) signaling pathway, reinforces EMT and ECM remodeling, further enhancing fibrotic progression. Adipocyte enhancer-binding protein 1 (AEBP1) and ZFP36 ring finger protein like 1 (ZFP36L1) also regulate inflammatory responses and ECM dynamics, providing novel post-transcriptional targets for therapeutic intervention. Overall, the synergistic interactions among these TFs create complex feedback loops that amplify pathological changes in PVDs. Targeting these molecular pathways offers promising avenues for developing multi-targeted therapies aimed at saving vision-threatening disease while reducing invasive surgical interventions.; (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. |
| Grant Information: | J.0128.23 Fonds De La Recherche Scientifique - FNRS; Fonds De La Recherche Scientifique - FNRS; 2022-J1820690-226884 King Baudouin Foundation; Fonds Erasme; Fonds pour la Recherche en Ophthalmologie; Vocatio |
| Contributed Indexing: | Keywords: Molecular biology; Proliferative vitreoretinal diseases; Retina; Review; Transcription factors |
| Entry Date(s): | Date Created: 20260508 Latest Revision: 20260508 |
| Update Code: | 20260509 |
| DOI: | 10.1186/s13578-026-01581-4 |
| PMID: | 42104523 |
| Database: | MEDLINE |
Journal Article; Review