Driving adult tissue repair via re-engagement of a pathway required for fetal healing.

Autor:	Ghatak S; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Khanna S; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Roy S; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Thirunavukkarasu M; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington, CT 06030, USA., Pradeep SR; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington, CT 06030, USA., Wulff BC; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., El Masry MS; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Plastic Surgery, Zagazig University, Zagazig 44519, Egypt., Sharma A; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Palakurti R; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Ghosh N; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Xuan Y; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA., Wilgus TA; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA., Maulik N; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington, CT 06030, USA., Yoder MC; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Sen CK; Indiana Center for Regenerative Medicine & Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: cksen@iu.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2023 Feb 01; Vol. 31 (2), pp. 454-470. Date of Electronic Publication: 2022 Sep 15.
DOI:	10.1016/j.ymthe.2022.09.002
Abstrakt:	Fetal cutaneous wound closure and repair differ from that in adulthood. In this work, we identify an oxidant stress sensor protein, nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), that is abundantly expressed in normal fetal epidermis (and required for fetal wound closure), though not in adult epidermis, but is variably re-induced upon adult tissue wounding. NPGPx is a direct target of the miR-29 family. Following injury, abundance of miR-29 is lowered, permitting a prompt increase in NPGPx transcripts and protein expression in adult wound-edge tissue. NPGPx expression was required to mediate increased keratinocyte migration induced by miR-29 inhibition in vitro and in vivo. Increased NPGPx expression induced increased SOX2 expression and β-catenin nuclear localization in keratinocytes. Augmenting physiologic NPGPx expression via experimentally induced miR-29 suppression, using cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides, proved to be sufficient to overcome the deleterious effects of diabetes on this specific pathway to enhance tissue repair. Competing Interests: Declaration of interests The authors declare no competing financial interests. (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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