Beck, PaulMacDonald, JustinAlhassan, Basmah Faris2014-07-182014-07-182014Alhassan, B. F. (2014). Protecting the gut against Clostridium difficile: A role for Keratinocyte growth factor (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27468http://hdl.handle.net/11023/1644Clostridium 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.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.ImmunologyMedicine and SurgeryPathologyClostridium difficileKeratinocyte growth factorKGFColitisIntestinal epithelial cellsClostridium difficile toxinsIntestinal trefoil factormaster thesis10.11575/PRISM/27468