Innate immune cell–epithelial crosstalk during wound repair

Abstract

2 9 8 4 jci.org Volume 129 Number 8 August 2019 degrade ECM components. Humans express 24 MMPs that regulate diverse activities important for ECM remodeling and forward movement of the epithelium (reviewed in ref. 19). MMP endoproteinase activity facilitates removal of disorganized structural proteins from healing wounds to make room for newly synthesized collagen. Furthermore, MMP-mediated conversion of type III collagen to more stable type I collagen increases wound tensile strength. Fibroblast-and keratinocyte-derived MMP-1 promotes breakdown of excess collagen in murine and rabbit models of skin repair (20-22). Though not expressed in skin, epithelial cellderived matrilysin (MMP-7) is reportedly the key MMP involved in repairing injured intestinal mucosa in humans (23, 24). Signals that trigger epithelial migration and proliferation from injured sites are incompletely understood. Loss or modification in cell-cell contact and release of intracellular molecules initiates repair (25). These events set the stage for recruiting leukocytes and mesenchymal cells that orchestrate wound repair. Formylated peptides and ATP released by damaged cells, also referred to as damage-associated molecular patterns (DAMPs), orchestrate repair by promoting epithelial cell migration and proliferation. Epithelial wounds are also a source of intracellular Ca ++ waves that are rapidly transmitted into surrounding tissues to influence repair. Furthermore, ROS signaling and wound-associated physical cues influence epithelial repair. Small GTPases in the Rho family regulate remodeling of F-actin, intercellular junctions, and cell-matrix adhesions (26) and are crucial for epithelial cell migration and wound sealing. Similarly, the Rho GTPase Rac1 promotes intestinal epithelial proliferation by targeting β 1-integrin in cellular protrusions and modulating actin dynamics (26). Reparative signaling events are also regulated by extracellular mediators in the epithelial milieu, including annexin A1, annexin A2, and serum amyloid A1, which have been shown to influence integrin localization, focal adhesion kinase activation, and cell matrix remodeling in mouse and human intestinal mucosa (27-30). After injury, chemokines/cytokines and growth factors play crucial roles in epithelial c ell adhesion, migration, proliferation, and differentiation. TGF-β-dependent signaling pathways mediate the regulatory effects of many repair mediators, including PDGF, EGF, VEGF, IL-1, IL-2, IL-6, and IFN-γ (6). Canonical and noncanonical Wnt proteins also modulate epithelial wound repair. A recent in vivo study revealed a role of Wnt5a in orchestrating colonic crypt

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

“…The immediate reaction to surgery, the acute inflammatory response, attracts immune cells and mesenchymal cells to the surgical field to assist in wound healing …”

Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration

“…Wound healing is a complex and well-orchestrated response to tissue injury and consists of four overlapping stages: hemostasis, inflammation, proliferation, and remodeling (Sun et al, 2014;Rodrigues et al, 2018). During tissue injury, the damaged cells release damage-associated molecular patterns and their intracellular contents that activate inflammasome and lead to the secretion of pro-inflammatory cytokines IL-1β and IL-18 (Saparov et al, 2017;Brazil et al, 2019). Platelets (PLTs) come in contact with the extracellular matrix and become activated, releasing clotting factors, promoting production of the matrix for migrating inflammatory cells, as well as various growth factors such as platelet-derived growth factor (PDGF), IL-1, TGF-α, and TGF-β that participate in wound healing (Saghazadeh et al, 2018;Brazil et al, 2019).…”

“…During tissue injury, the damaged cells release damage-associated molecular patterns and their intracellular contents that activate inflammasome and lead to the secretion of pro-inflammatory cytokines IL-1β and IL-18 (Saparov et al, 2017;Brazil et al, 2019). Platelets (PLTs) come in contact with the extracellular matrix and become activated, releasing clotting factors, promoting production of the matrix for migrating inflammatory cells, as well as various growth factors such as platelet-derived growth factor (PDGF), IL-1, TGF-α, and TGF-β that participate in wound healing (Saghazadeh et al, 2018;Brazil et al, 2019). PDGF, IL-1, IL-18, and other pro-inflammatory cytokines attract neutrophils to the injury site where they secrete proteases, reactive oxygen species, and phagocytose cell debris and pathogens, if present (Jorch and Kubes, 2017).…”

“…Moreover, recruited neutrophils secrete TNF-α, IL-1, IL-6, and chemokines that stimulate migration of the cells of the immune system, including monocytes (Castano et al, 2018). Recruited monocytes differentiate into either pro-inflammatory macrophages, which produce TNFα, IL-1β, or reparative macrophages, which secrete IL-10 and TGF-β (Brazil et al, 2019). Macrophages also phagocytose the remaining debris and apoptotic neutrophils, as well as stimulate fibroblast infiltration.…”

Polysaccharide-Based Formulations for Healing of Skin-Related Wound Infections: Lessons from Animal Models and Clinical Trials

“…Wound healing is a complex biochemical and cellular process consisting of sequential and overlapping phases (hemostasis, inflammatory, proliferative, and remodeling stages) that occur in response to the physical disruption of tissue [1,2]. Skin injuries constitute a gateway for Based on [13][14][15][16][17][18][19].…”