Browsing by Subject "Keratinocyte migration"

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    Driving adult tissue repair via re-engagement of a pathway required for fetal healing
    (Elsevier, 2023) Ghatak, Subhadip; Khanna, Savita; Roy, Sashwati; Thirunavukkarasu, Mahesh; Pradeep, Seetur R.; Wulff, Brian C.; El Masry, Mohamed S.; Sharma, Anu; Palakurti, Ravichand; Ghosh, Nandini; Xuan, Yi; Wilgus, Traci A.; Maulik, Nilanjana; Yoder, Mervin C.; Sen, Chandan K.; Surgery, School of Medicine
    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.