Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury

dc.contributor.authorSripathi M. Sureban
dc.contributor.authorRandal May
dc.contributor.authorDongfeng Qu
dc.contributor.authorParthasarathy Chandrakesan
dc.contributor.authorNathaniel Weygant
dc.contributor.authorNaushad Ali
dc.contributor.authorStan A. Lightfoot
dc.contributor.authorKai Ding
dc.contributor.authorShahid Umar
dc.contributor.authorMichael J. Schlosser
dc.contributor.authorCourtney W. Houchen
dc.date.accessioned2017-03-05T22:55:07Z
dc.date.available2017-03-05T22:55:07Z
dc.date.issued2015-08-13
dc.descriptionThis research was performed as a project of the Intestinal Stem Cell Consortium, a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIH U01 DK-085508 to CWH), and a grant from Oklahoma Center for the Advancement of Science and Technology to CWH.en_US
dc.descriptionen_US
dc.description.abstractGastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationSureban SM, May R, Qu D, Chandrakesan P, Weygant N, Ali N, et al. (2015) Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury. PLoS ONE 10(8): e0135561. doi:10.1371/journal.pone.0135561en_US
dc.identifier.doi10.1371/journal.pone.0135561en_US
dc.identifier.urihttp://hdl.handle.net/11244/49267
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(8): e0135561
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0135561
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectPectins,Gastrointestinal tract,Diet,Cancer treatment,Radiation therapy,Infrared radiation,Stem cell therapy,Small intestineen_US
dc.titleDietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injuryen_US
dc.typeResearch Articleen_US

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