Browsing by Author "Alhassan, Basmah Faris"

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    Protecting the gut against Clostridium difficile: A role for Keratinocyte growth factor
    (2014-07-18) Alhassan, Basmah Faris; Beck, Paul; MacDonald, Justin
    Clostridium difficle (Cdiff) infection (CDI) causes severe colitis via its toxins: toxin A and toxin B (TcdAB), inducing barrier disruption, inflammation and cell death. Current treatments are failing and the need to search for new targets is urgent. Several host factors have shown to modulate CDI in animals and patients. Intestinal growth factors are a major part of the mucosal host response in the gut. Among them, keratinocyte growth factor (KGF) has been shown to be protective in many colitis models. In this thesis, the protective role of KGF was demonstrated against Cdiff toxin injury. In vitro, KGF protected Caco-2 cells from barrier disruption and cell death induced by TcdAB. Exogenous KGF administration protected mice from acute intestinal toxin damage. Interestingly, KGF deletion did not impact the acute toxin-induced colitis in mice; however, endogenous KGF was essential for normal recovery from TcdAB-induced colitis as KGF−/− mice demonstrated impaired recovery after 24-48 hours post TcdAB exposure. Findings from this study may lead to identifying a cause for the variability in clinical response among patients with CDI as well as new therapeutic targets for this devastating disease.