title: Radiotherapy-induced gut toxicity: Involvement of matrix metalloproteinases and the intestinal microvasculature.
abstract: Purpose To review the literature surrounding the involvement of the endothelium and matrix metalloproteinases (MMP) in radiotherapy-induced gut toxicity (RIGT) and further elucidate its complex pathobiology. Results RIGT involves damage to the gastrointestinal mucosa and is associated with diarrhoea, pain, and rectal bleeding depending on the area of exposure. The mechanisms underpinning RIGT are complex and have not yet been elucidated. Members of the MMP family, particularly MMP-2 and -9, have recently been identified as being key markers in RIGT and chemotherapy-induced gut toxicity (CIGT). Furthermore, the microvasculature has long been implicated in the development of toxicities following both chemotherapy and radiotherapy, however, the mechanisms behind this are yet to be explored. Conclusions It is proposed that matrix metalloproteinases are key regulators of endothelial mediators, and may play a key role in inducing damage to intestinal microvasculature following radiotherapy.
authors.affiliation: a School of Medicine , University of Adelaide , Adelaide , Australia.
authors.forename: Romany L
authors.initials: RL
authors.lastname: Stansborough
authors.affiliation: a School of Medicine , University of Adelaide , Adelaide , Australia.
authors.forename: Noor
authors.initials: N
authors.lastname: Al-Dasooqi
authors.affiliation: a School of Medicine , University of Adelaide , Adelaide , Australia.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Bateman
authors.affiliation: a School of Medicine , University of Adelaide , Adelaide , Australia.
authors.forename: Dorothy M K
authors.initials: DM
authors.lastname: Keefe
authors.affiliation: a School of Medicine , University of Adelaide , Adelaide , Australia.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Gibson
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D019317:Evidence-Based Medicine; D005767:Gastrointestinal Diseases / Q000201:enzymology* / Q000209:etiology*; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D055806:Microvessels / Q000528:radiation effects*; D011832:Radiation Injuries / Q000201:enzymology* / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage
chemical_list: D020782:Matrix Metalloproteinases
keywords: Mucositis; endothelium; gastrointestinal; metalloproteinases; radiotherapy