Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts

Abstract Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair proc...

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Autores principales:	Gokhan Gundogdu, Mehmet Tosun, Duncan Morhardt, Ali Hashemi Gheinani, Khalid Algarrahi, Xuehui Yang, Kyle Costa, Cinthia Galvez Alegria, Rosalyn M. Adam, Wei Yang, Joshua R. Mauney
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a157cec5dad4acf8cdc10f9a17b86f5
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spelling	oai:doaj.org-article:1a157cec5dad4acf8cdc10f9a17b86f52021-12-02T14:25:09ZMolecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts10.1038/s41598-021-86511-92045-2322https://doaj.org/article/1a157cec5dad4acf8cdc10f9a17b86f52021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86511-9https://doaj.org/toc/2045-2322Abstract Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.Gokhan GundogduMehmet TosunDuncan MorhardtAli Hashemi GheinaniKhalid AlgarrahiXuehui YangKyle CostaCinthia Galvez AlegriaRosalyn M. AdamWei YangJoshua R. MauneyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gokhan Gundogdu Mehmet Tosun Duncan Morhardt Ali Hashemi Gheinani Khalid Algarrahi Xuehui Yang Kyle Costa Cinthia Galvez Alegria Rosalyn M. Adam Wei Yang Joshua R. Mauney Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
description	Abstract Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.
format	article
author	Gokhan Gundogdu Mehmet Tosun Duncan Morhardt Ali Hashemi Gheinani Khalid Algarrahi Xuehui Yang Kyle Costa Cinthia Galvez Alegria Rosalyn M. Adam Wei Yang Joshua R. Mauney
author_facet	Gokhan Gundogdu Mehmet Tosun Duncan Morhardt Ali Hashemi Gheinani Khalid Algarrahi Xuehui Yang Kyle Costa Cinthia Galvez Alegria Rosalyn M. Adam Wei Yang Joshua R. Mauney
author_sort	Gokhan Gundogdu
title	Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
title_short	Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
title_full	Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
title_fullStr	Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
title_full_unstemmed	Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
title_sort	molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1a157cec5dad4acf8cdc10f9a17b86f5
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Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts

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