Deletion of cystathionine-γ-lyase in bone marrow-derived cells promotes colitis-associated carcinogenesis
Graphical abstract
Downregulation of CSE expression and/or activity promotes excessive inflammation in the gut resulting in the development of CAC. A schematic model of colon epithelial cell function under conditions of (a) increased and (b) decreased CSE activity. (a) In physiological conditions, intact CSE function is critical in limiting mucosal inflammation and stimulating the permeability, cellular mobility, and proliferation of the colon epithelial layer in response to injury. (b) Loss or inhibition of CSE impairs transepithelial permeability, cell migration, and proliferation, accelerating both the development and progression of CAC. An altered cytokine profile of the pro-and anti-inflammatory mediators in colon mucosa has been suggested to play a critical role in the development of CAC. Several of these alterations, including reduced IL-10 and increased IL-6 expression levels may be initiated by the lack of CSE activity in BM-derived cells.
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- 1
These authors contributed equally to this work.
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Laboratoire Ecologie & Biologie des Interactions, UMR CNRS 7267 Université de Poitiers, 86,000 Poitiers, France.
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Mechanisms of Carcinogenesis Program, Division of Gastroenterology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.