Intestinal mucosal wound resealing

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

↗ Live URL (may be dead)

Document text

Principal Investigator: ASMA  NUSRAT
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2021
Award: $460,345
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases

Abstract
The gastrointestinal epithelium plays a central role in maintaining and coordinating mucosal homeostasis and
immunity. Intestinal epithelial barrier compromise in mucosal wounds is seen in many pathologic states that
encompass inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. Coordinated
epithelial cell migration and proliferation are crucial for mucosal wound closure, yet many aspects of this
complex process are not well understood. Mucosal reparative events are orchestrated by the epithelium itself
as well as by a spatiotemporal interplay of epithelial-immune cell cross-talk. Select inflammatory cytokines
initiate synthesis of mediators that not only serve to influence the inflammatory cascade but also dismantle it
and promote repair. The overarching hypothesis is that temporal recruitment and activation of immune cells
into injured sites influence epithelial signaling to promote repair. Thus, the proposed studies will identify and
characterize mechanisms by which immune cell derived mediators influence and regulate intestinal epithelial
wound repair. Knowledge gained from these studies in the short term will provide a better understanding of
basic mechanisms by which inflammatory cell and epithelial mediators control intestinal epithelial homeostasis
and mucosal wound repair. In the long term these studies will aid in the development of new therapeutic
strategies aimed at promoting intestinal mucosal wound repair.

Terms: <(TNF)-α><Address><Alimentary Canal><Antibodies><Assay><Autoregulation><Bioassay><Biologic Assays><Biological Assay><Biopsy><Body Tissues><Bone Marrow Grafting><Bone Marrow Transplant><Bone Marrow Transplantation><C-KIT Gene><CD117><CD117 Antigens><CHEMERINR><CHEMR23><CMKLR1><CMKLR1 gene><Cachectin><Cell Body><Cell Communication and Signaling><Cell Growth in Number><Cell Line><Cell Locomotion><Cell Migration><Cell Movement><Cell Multiplication><Cell Proliferation><Cell Signaling><Cell Survival><Cell Viability><CellLine><Cells><Cellular Migration><Cellular Motility><Cellular Proliferation><Chemerin Receptor><Chemokine Like Receptor 1><Colitis><Colonoscopy><Complex><Data><Development><Digestive Tract><Encapsulated><Epithelial><Epithelial Cells><Event><G Protein-Complex Receptor><G Protein-Coupled Receptor Genes><G-Protein-Coupled Receptors><GI Tract><GPCR><Gastrointestinal Tract><Gastrointestinal tract structure><Generations><Grant><Gut Epithelium><Homeostasis><IFN><Immune><Immune Cell Activation><Immunes><Immunity><In Vitro><Inflammation><Inflammation Mediators><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Inflammatory Response><Injury><Interferons><Intestinal Mucosa><Intracellular Communication and Signaling><Ischemia><KO mice><Knock-out Mice><Knockout Mice><Knowledge><Ligands><Light><Link><Lipids><Longitudinal Studies><Lymphoid Cell><MGF Stem Cell Factor><Macrophage-Derived TNF><Marrow Mast Cell><Marrow Transplantation><Mast Cell Growth Factor><Mast Cell Growth Factor Receptor><Mechanics><Mediating><Mediator><Mediator of Activation><Mediator of activation protein><Mice><Mice Mammals><Modeling><Monocyte-Derived TNF><Motility><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Null Mouse><Operative Procedures><Operative Surgical Procedures><Pathologic><Peripheral><Photoradiation><Physiological Homeostasis><Play><Polymers><Process><Property><Proteins><Proto-Oncogene Protein c-kit><RNA Splicing><Receptor Protein><Recovery><Reporting><Role><SCF Receptor><SCF Receptor Gene><SCFR><Secondary to><Signal Transduction><Signal Transduction Systems><Signaling><Site><Splicing><Steel Factor><Stem Cell Factor><Stem Cell Factor Receptor><Stem Cell Factor Receptor Gene><Strains Cell Lines><Surgical><Surgical Interventions><Surgical Procedure><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Therapeutic><Tissue Basophils><Tissues><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Variant><Variation><Wound Repair><alimentary tract><base><biological signal transduction><c kit><c-kit Ligand><c-kit Protein><c-kit Receptor><cell motility><cultured cell line><cytokine><developmental><digestive canal><epithelial wound><experiment><experimental research><experimental study><gastrointestinal epithelium><healing><immune activation><improved><in vivo><inflammatory mediator><inhibiting antibody><injured><injuries><intestinal epithelium><kit Ligand><kit Proto-Oncogene Protein><lipid mediator><lipidomics><long-term study><longitudinal outcome studies><longterm study><mast cell><mastocyte><mechanical><migration><nano particle><nano-sized particle><nanoparticle><nanosized particle><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><novel><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><p145(c-kit)><p145c-kit><receptor><recruit><repair><repaired><response><social role><spatiotemporal><surgery><tissue wound><wound><wound closure><wound healing><wound resolution><wounding><wounds>