Abstract
Toll-like receptors (TLRs) are innate receptors critical for host defense, and play a role in normal biological processes. For example, host DNA, a TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays a crucial role in regulating intestinal homeostasis. We therefore asked whether TLR9 is important for intestinal wound repair using a dextran sulfate sodium (DSS)-induced intestinal damage and repair model. We showed that TLR9-deficient mice are more susceptible to DSS, and exhibited delayed wound repair at both the clinical and histologic levels. TLR9-deficient mice showed reduced gene expression of hairy enhancer of split 1, an intestinal progenitor cell differentiation factor, and vascular endothelial growth factor, a growth factor important for epithelial cell restitution. Therefore, we conclude that TLR stimulation may play a normal role in regulating intestinal homeostasis and could potentially be a novel therapeutic target to enhance intestinal wound repair in inflammatory bowel diseases.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Differentiation / genetics
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Cell Proliferation
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Colon / metabolism
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Colon / pathology
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Enterocytes / metabolism
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Female
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Genetic Predisposition to Disease
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Inflammatory Bowel Diseases / genetics
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / pathology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology*
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Leukocytes / immunology
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Leukocytes / pathology
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Mice
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Mice, Knockout
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Signal Transduction
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Stem Cells / cytology
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Stem Cells / metabolism
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Toll-Like Receptor 9 / genetics*
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Toll-Like Receptor 9 / immunology
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Transcription Factor HES-1
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Vascular Endothelial Growth Factor A / metabolism
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Wound Healing / genetics*
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Wound Healing / immunology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Hes1 protein, mouse
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Homeodomain Proteins
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Toll-Like Receptor 9
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Transcription Factor HES-1
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Vascular Endothelial Growth Factor A