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Toll-like receptors, wound healing, and carcinogenesis

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Abstract

Following acute injury, the concerted action of resident and nonresident cell populations evokes wound healing responses that entail a temporary increase in inflammation, extracellular matrix production, and proliferation to ultimately restore normal organ architecture. However, chronic injury evokes a perpetuating wound healing response promoting the development of fibrosis, organ failure, and cancer. Recent evidence points toward toll-like receptors (TLRs) as important regulators of inflammatory signals in wound healing. Here, we will review the activation of TLRs by different endogenous and bacterial TLR ligands during wound healing, and the contribution of TLR-induced signals to injury, fibrogenesis, regeneration, and carcinogenesis. We will discuss the hypothesis that TLRs act as sensors of danger signals in injured tissue to switch the wound healing response toward fibrogenesis and regeneration as a protective response to imminent danger at the cost of an increased long-term risk of developing scars and cancer.

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Acknowledgements

Johannes Kluwe was supported by a postdoctoral fellowship from the American Liver Foundation. Robert F. Schwabe was supported by grants R01DK076920-01A2 and U54CA126513 from the National Institutes of Health.

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Kluwe, J., Mencin, A. & Schwabe, R.F. Toll-like receptors, wound healing, and carcinogenesis. J Mol Med 87, 125–138 (2009). https://doi.org/10.1007/s00109-008-0426-z

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  • DOI: https://doi.org/10.1007/s00109-008-0426-z

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