An orientation-independent DIC microscope allows high resolution imaging of epithelial cell migration and wound healing in a cnidarian model

The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell–cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.

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Rho kinase modulates the actin cytoskeleton in intestinal epithelial cells and is essential for epithelial cell migration during wound healing

Gastroenterology ◽

10.1016/s0016-5085(00)85447-5 ◽

2000 ◽

Vol 118 (4) ◽

pp. A826

Author(s):

Shaun V. Walsh ◽

Ann M. Hopkins ◽

Christie T. Vu ◽

Charles A. Parkos ◽

Asma Nusrat

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Epithelial Cell ◽

Epithelial Cells ◽

Actin Cytoskeleton ◽

Intestinal Epithelial Cells ◽

Rho Kinase ◽

Intestinal Epithelial ◽

Epithelial Cell Migration

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Emerin regulation of nuclear stiffness is required for the amoeboid migration of cancer cells in confining environments

10.1101/2020.06.15.153007 ◽

2020 ◽

Author(s):

Sandrine B. Lavenus ◽

Karl W. Vosatka ◽

Maria F. Ullo ◽

Jeremy S. Logue

Keyword(s):

Cell Migration ◽

High Resolution ◽

Cancer Cells ◽

Nuclear Membrane ◽

High Resolution Imaging ◽

Cell Deformability ◽

Inner Nuclear Membrane ◽

Resolution Imaging

AbstractThrough the process of regulating cell deformability in confined environments, the nucleus has emerged as a major regulator of cell migration. Here, we demonstrate that nuclear stiffness regulates the confined (leader bleb-based) migration of cancer cells. Using high-resolution imaging, we demonstrate that modifying the level of the Inner Nuclear Membrane (INM) protein, emerin, will inhibit Leader Bleb-Based Migration (LBBM). In line with the notion that nuclear stiffness regulates LBBM, stiffness measurements indicate that nuclei are softest at endogenous levels of emerin. Emerin has been found to be phosphorylated by Src in response to force, increasing nuclear stiffness. Accordingly, we found LBBM to be insensitive to increasing levels of emerin (Y74F/Y95F). Using a biosensor, Src activity is found to negatively correlate with cell confinement. Thus, our data are consistent with a model in which low Src activity maintains a soft nucleus and promotes the confined (leader bleb-based) migration of cancer cells.

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Abstract B18: Expression of CTIP2/Bcl11b is linked to disease progression in head and neck cancer and is a critical mediator of epithelial cell migration and motility during wound healing processes

10.1158/1078-0432.tcmusa10-b18 ◽

2010 ◽

Author(s):

Gaurav Bajaj ◽

Jang Hyo-Sang ◽

Talicia Savage ◽

Xiaobo Liang ◽

Mark Leid ◽

...

Keyword(s):

Wound Healing ◽

Head And Neck Cancer ◽

Cell Migration ◽

Epithelial Cell ◽

Head And Neck ◽

Disease Progression ◽

Neck Cancer ◽

Epithelial Cell Migration ◽

Healing Processes

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CXCL12 activation of CXCR4 regulates mucosal host defense through stimulation of epithelial cell migration and promotion of intestinal barrier integrity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00208.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. G316-G326 ◽

Cited By ~ 50

Author(s):

Jennifer M. Smith ◽

Priscilla A. Johanesen ◽

Michael K. Wendt ◽

David G. Binion ◽

Michael B. Dwinell

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Epithelial Cell ◽

Host Defense ◽

Intestinal Epithelial Cell ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Barrier Integrity ◽

Epithelial Migration ◽

Epithelial Cell Migration

Intestinal epithelial cell migration plays a key role in gastrointestinal mucosal barrier formation, enterocyte development, differentiation, turnover, wound healing, and adenocarcinoma metastasis. Chemokines, through engagement of their corresponding receptors, are potent mediators of directed cell migration and are critical in the establishment and regulation of innate and adaptive immune responses. The aim of this study was to define the role for the chemokine CXCL12 and its sole cognate receptor CXCR4 in regulating intestinal epithelial cell migration and to determine its impact on barrier integrity. CXCL12 stimulated the dose-dependent chemotactic migration of human T84 colonic epithelial cells. Epithelial cell migration was inhibited by CXCR4 neutralizing antibody, pertussis toxin, LY-294002, and PD-98059, thereby implicating Gαi, phosphatidylinositol 3-kinase (PI3-kinase), and the ERK1/2 MAP kinase pathways in CXCR4-specific signaling. CXCL12 was also shown to increase barrier integrity, as defined by transepithelial resistance and paracellular flux across differentiating T84 monolayers. To determine whether CXCL12 regulated epithelial restitution, we used the normal nontransformed intestinal epithelial cell-6 (IEC-6) wound healing model. By using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, we first showed expression of both CXCR4 and its ligand by IEC-6 cells. We then demonstrated that CXCL12 activated comparable signaling mechanisms to stimulate epithelial migration in the absence of proliferation in wounded IEC-6 monolayers. Taken together, these data indicate that CXCL12 signaling via CXCR4 directs intestinal epithelial cell migration, barrier maturation, and restitution, consistent with an important mechanistic role for these molecules in mucosal barrier integrity and innate host defense.

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Resolvin E1 is a pro-repair molecule that promotes intestinal epithelial wound healing

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1921335117 ◽

2020 ◽

Vol 117 (17) ◽

pp. 9477-9482 ◽

Cited By ~ 5

Author(s):

Miguel Quiros ◽

Darius Feier ◽

Dorothee Birkl ◽

Rachit Agarwal ◽

Dennis W. Zhou ◽

...

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Epithelial Cell ◽

Wound Repair ◽

Intestinal Epithelial Cell ◽

Intestinal Inflammation ◽

Small Gtpase ◽

Intestinal Epithelial ◽

Epithelial Cell Migration ◽

Cell Migration And Proliferation

Resolution of intestinal inflammation and wound repair are active processes that mediate epithelial healing at mucosal surfaces. Lipid molecules referred to as specialized proresolving mediators (SPMs) play an important role in the restorative response. Resolvin E1 (RvE1), a SPM derived from omega-3 fatty acids, has been reported to dampen intestinal inflammation by promoting anti-inflammatory responses including increased neutrophil spherocytosis and macrophage production of IL-10. Despite these observations, a role for RvE1 in regulating intestinal epithelial cell migration and proliferation during mucosal wound repair has not been explored. Using an endoscopic biopsy-based wound healing model, we report that RvE1 is locally produced in response to intestinal mucosal injury. Exposure of intestinal epithelial cells to RvE1 promoted wound repair by increasing cellular proliferation and migration through activation of signaling pathways including CREB, mTOR, and Src-FAK. Additionally, RvE1-triggered activation of the small GTPase Rac1 led to increased intracellular reactive oxygen species (ROS) production, cell–matrix adhesion, and cellular protrusions at the leading edge of migrating cells. Furthermore, in situ administration of RvE1-encapsulated synthetic targeted polymeric nanoparticles into intestinal wounds promoted mucosal repair. Together, these findings demonstrate that RvE1 functions as a prorepair lipid mediator by increasing intestinal epithelial cell migration and proliferation, and highlight potential therapeutic applications for this SPM to promote mucosal healing in the intestine.

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