Effects of TGF-alpha gene knockout on epithelial cell kinetics and repair of methotrexate-induced damage in mouse small intestine

Journal of Cellular Physiology
Cory J XianL C Read

Abstract

While previous studies have indicated that exogenous TGF-alpha stimulates epithelial growth, maintenance, and repair of the gut, roles of endogenous TGF-alpha are less well-defined particularly in the small bowel. The current study examined effects of TGF-alpha knockout on adult small intestinal epithelial cell proliferation, migration, apoptosis, and damage/repair response after methotrexate treatment. Compared to normal mice, TGF-alpha gene knockout did not affect crypt cell production, mitosis position, migration, and apoptosis in non-injured intestine. RT-PCR gene expression analysis revealed presence of four out of six TGF-alpha related EGF family ligands in the normal intestine, suggesting a possible functional redundancy of the EGF family in maintenance of the intestine. Although TGF-alpha gene knockout did not significantly impair the overall mucosal repair in methotrexate-induced acute damage in the small intestine, it resulted in a higher apoptotic response in the early hours following methotrexate challenge, and a delayed and reduced crypt cell proliferation during repair. Consistently, after methotrexate challenge, intestinal TGF-alpha mRNA was found to be markedly upregulated in the early hours and during repair in...Continue Reading

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Citations

Mar 28, 2006·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Rajesh V LallaDorothy Keefe
Jan 20, 2009·World Journal of Gastroenterology : WJG·Laurie Drozdowski, Alan B R Thomson
Mar 27, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Mi-Hyun KangYoungsook Son
Aug 5, 2006·Journal of Cellular Biochemistry·Cory J XianBruce K Foster
Jul 31, 2008·Journal of Pediatric Gastroenterology and Nutrition·Igor SukhotnikRaanan Shamir
Aug 15, 2013·British Journal of Pharmacology·Tatsuro NakamuraHiroshi Ozaki
Jan 24, 2019·Mediators of Inflammation·Sandra Rayego-MateosMarta Ruiz-Ortega

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis