DNA Methylation Dynamics During Esophageal Epithelial Regeneration Following Repair with Acellular Silk Fibroin Grafts in Rat.

Autor: Urban LA; Department of Microbiology & Molecular Genetics, University of California Irvine, Irvine, CA, 92697, USA.; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California-Irvine, Irvine, CA, 92697, USA., Li J; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California-Irvine, Irvine, CA, 92697, USA.; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA., Gundogdu G; Department of Urology, University of California, Orange, Irvine, CA, 92868, USA., Trinh A; Department of Microbiology & Molecular Genetics, University of California Irvine, Irvine, CA, 92697, USA.; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California-Irvine, Irvine, CA, 92697, USA.; The NSF-Simons Center for Multiscale Cell Fate Research, University of California-Irvine, Irvine, CA, 92697, USA., Shao H; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California-Irvine, Irvine, CA, 92697, USA.; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA., Nguyen T; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA., Mauney JR; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA.; Department of Urology, University of California, Orange, Irvine, CA, 92868, USA., Downing TL; Department of Microbiology & Molecular Genetics, University of California Irvine, Irvine, CA, 92697, USA.; UCI Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center (CIRC), University of California-Irvine, Irvine, CA, 92697, USA.; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA.; The NSF-Simons Center for Multiscale Cell Fate Research, University of California-Irvine, Irvine, CA, 92697, USA.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2023 May; Vol. 7 (5), pp. e2200160. Date of Electronic Publication: 2023 Jan 19.
DOI: 10.1002/adbi.202200160
Abstrakt: Esophageal pathologies such as atresia and benign strictures often require surgical reconstruction with autologous tissues to restore organ continuity. Complications such as donor site morbidity and limited tissue availability have spurred the development of acellular grafts for esophageal tissue replacement. Acellular biomaterials for esophageal repair rely on the activation of intrinsic regenerative mechanisms to mediate de novo tissue formation at implantation sites. Previous research has identified signaling cascades involved in neoepithelial formation in a rat model of onlay esophagoplasty with acellular silk fibroin grafts, including phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling. However, it is currently unknown how these mechanisms are governed by DNA methylation (DNAme) during esophageal wound healing processes. Reduced-representation bisulfite sequencing is performed to characterize temporal DNAme dynamics in host and regenerated tissues up to 1 week postimplantation. Overall, global hypermethylation is observed at postreconstruction timepoints and an inverse correlation between promoter DNAme and the expression levels of differentially expressed proteins during regeneration. Site-specific hypomethylation targets genes associated with immune activation, while hypermethylation occurs within gene bodies encoding PI3K-Akt signaling components during the tissue remodeling period. The data provide insight into the epigenetic mechanisms during esophageal regeneration following surgical repair with acellular grafts.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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