Small Molecule Screen Identifies Elafibranor To Protect Irf6-dependent Epithelial Integrity

Small Molecule Screen Identifies Elafibranor To Protect Irf6-dependent Epithelial Integrity | Zenodo Skip to main Communities My dashboard Log in Sign up Zenodo is currently experiencing slowness and intermittent outages due to heavy automated traffic from bots and AI crawlers. We are aware of the problem, and our team is focused on stabilizing the service. Thank you for your patience. 71st Annual Meeting Plastic Surgery Research Council - Los Angeles, California There is a newer version of the record available. Published May 8, 2026 | Version v2 Conference paper Open Small Molecule Screen Identifies Elafibranor To Protect Irf6-dependent Epithelial Integrity Authors/Creators Helen Molteni 1 Brandi Golden 2 Emily Yu 2 Eric Liao Show affiliations 1.

Children's Hospital of Philadelphia, Philadelphia, PA, USA,; Perelman School of Medicine, Philadelphia, PA, USA, 2.

Children's Hospital of Philadelphia, Philadelphia, PA, USA, Description PURPOSE: Interferon regulatory factor 6 (IRF6) is a key genetic driver of orofacial clefts and master regulator of epithelial biology. During midface development, IRF6 maintains skin barrier integrity and prevents abnormal epithelial adhesions from interfering with palatal shelf fusion. In addition to its role in palatogenesis, IRF6 is a major regulator of reepithelization during wound healing. Recent in vitro findings demonstrated enhanced IRF6 activity upon binding to glucose, suggesting a potential link between carbohydrate metabolism and IRF6-mediated epithelial differentiation. METHODS: 572 small molecules with known influence in carbohydrate metabolism were screened using the irf6 maternal-null ( irf6 m-null ) zebrafish model. Expression of epithelial differentiation markers were measured at multiple developmental stages using qPCR. Immunofluorescence was performed to visualize epithelial enveloping layer (EVL) architecture, cell morphology, and tight junction localization. Epithelial surface topography was visualized from scanning election microscopy. Alcian blue staining was employed to evaluate craniofacial structures. RESULTS: Elafibranor, a dual PPARα/PPARd agonist, delayed rupture and rescued irf6 m-null embryos from rupture at onset of gastrulation. Elafibranor partially restored EVL cell shape, localization of junctional protein Zo1, and cell-cell contacts to facilitate stretching of the layer. Expression of epithelial differentiation markers tp63 , cebpb , and esrp1 were partially restored by elafibranor treatment. Surprisingly, EVL structural changes occurred before changes in differentiation gene expression, suggesting that intercellular mechanical forces promoting adhesion influence IRF6-mediated epithelial differentiation. Further, elafibranor-exposed wildtype zebrafish displayed characteristics of exacerbated adhesion, including craniofacial cartilage dysmorphology and structural surface alterations to the developing skin barrier. CONCLUSION: This study contributes a novel finding that a small molecule elafibranor partially restored IRF6-dependent epithelial differentiation with effects on epithelial integrity and craniofacial morphology. This work elucidates how IRF6 may regulate epithelial function through regulation of tight junctions to allow for cell movement. Given elafibranor's protective role in this process, it may hold promise for downstream clinical applications in mitigating cleft pathogenesis and preserving epithelial barrier integrity.

*Source: https://ps-rc.org/meeting/Program/2026/26.cgi* Notes Abstract ID: 26 Files PSRC2026_26.txt Files (3.4 kB) Name Size Download all PSRC2026_26.txt md5:2cde16cb9100b0de7eed6c20d38d83ba 3.4 kB Preview Download 96 Views 20 Downloads Show more details All versions This version Views Total views 96 16 Downloads Total downloads 20 5 Data volume Total data volume 68.6 kB 17.2 kB More info on how stats are collected.... Versions External resources Indexed in OpenAIRE Communities Keywords and subjects Keywords plastic surgery reconstructive surgery conference abstract PSRC 2026 Details DOI DOI Badge DOI 10.5281/zenodo.20078542 Markdown [](https://doi.org/10.5281/zenodo.20078542) reStructuredText .. image:: https://zenodo.org/badge/DOI/10.5281/zenodo.20078542.svg :target: https://doi.org/10.5281/zenodo.20078542 HTML <a href="https://doi.org/10.5281/zenodo.20078542"><img src="https://zenodo.org/badge/DOI/10.5281/zenodo.20078542.svg" alt="DOI"></a> Image URL https://zenodo.org/badge/DOI/10.5281/zenodo.20078542.svg Target URL https://doi.org/10.5281/zenodo.20078542 Resource type Conference paper Publisher Zenodo Conference 71st Annual Meeting of the Plastic Surgery Research Council (PSRC 2026), Los Angeles, CA, USA, June 4-7, 2026 Rights License Creative Commons Attribution Non Commercial No Derivatives 4.0 International No further description. Read more Citation Export Technical metadata Created May 8, 2026 Modified May 8, 2026 Jump up About About Policies Infrastructure Principles Projects Roadmap Contact Blog Blog Support Help FAQ Developers REST API OAI-PMH Contribute GitHub Donate Funded by Powered by CERN Data Centre & InvenioRDM Status Privacy policy Cookie policy Terms of Use This site uses cookies. Find out more on how we use cookies Accept all cookies Accept only essential cookies

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