Intestinal epithelial cell (IEC) cycle arrest has recently been found to be involved in the pathogenesis of Crohn's disease (CD). However, the mechanism underlying the regulation of this form of cell cycle arrest, remains unclear. Here, we investigated the roles that advanced oxidation protein products (AOPPs) may play in regulating IEC cycle arrest. Plasma AOPPs levels and IEC cycle distributions were evaluated in 12 patients with CD. Molecular changes in various cyclins, cyclin-dependent kinases (CDKs), and other regulatory molecules were examined in cultured immortalized rat intestinal epithelial (IEC-6) cells after treatment with AOPPs. The in vivo effects exerted by AOPPs were evaluated using a normal C57BL/6 mouse model with an acute AOPPs challenge. Interestingly, plasma AOPPs levels were elevated in active CD patients and correlated with IEC G1 phase arrest. In addition, IEC treatment with AOPPs markedly reduced the expression of cyclin E and CDK2, thus sensitizing epithelial cells to cell cycle arrest both in vitro and in vivo. Importantly, we found that AOPPs induced IEC G1 phase arrest by modulating two membrane receptors, RAGE and CD36. Furthermore, phosphorylation of c-jun N-terminal kinase (JNK) and the expression of p27kip1 in AOPPs-treated cells were subsequently increased and thus affected cell cycle progression. Our findings reveal that AOPPs influence IEC cycle progression by reducing cyclin E and CDK2 expression through RAGE/CD36-depedent JNK/p27kip1 signaling. Consequently, AOPPs may represent a potential therapeutic molecule. Targeting AOPPs may offer a novel approach to managing CD.

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Inflammatory bowel disease (IBD) is a chronic and life-long disease, and patients must ultimately learn to live with and manage the condition. With advances in diagnostics and treatment in IBD, healthcare professionals (HCP) and patients are now concerned with both quality of care (QOC) and quality of life (QOL). China Crohn’s and Colitis Foundation (CCCF) is committed to improving the QOC and QOL for IBD patients by garnering social resources. This paper details how CCCF has worked for better IBD management over the past five years. The foundation has four main projects: education programs for IBD HCPs and patients, support activities, public awareness and advocacy, and research programs. CCCF is an increasingly influential public welfare organization providing advocacy for IBD patients in China. The foundation is now entering the next stage of its development in pursuing professional operations and helping to solve the social problems experienced by IBD patients. CCCF ultimately plans to pioneer reforms in China’s medical system and hopefully provide a successful example of IBD advocacy for developing countries to emulate.

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