| First Author | Udden SMN | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 13 | Pages | 2756-2770 |
| PubMed ID | 28658623 | Mgi Jnum | J:254357 |
| Mgi Id | MGI:6102966 | Doi | 10.1016/j.celrep.2017.05.084 |
| Citation | Udden SMN, et al. (2017) NOD2 Suppresses Colorectal Tumorigenesis via Downregulation of the TLR Pathways. Cell Rep 19(13):2756-2770 |
| abstractText | Although NOD2 is the major inflammatory bowel disease susceptibility gene, its role in colorectal tumorigenesis is poorly defined. Here, we show that Nod2-deficient mice are highly susceptible to experimental colorectal tumorigenesis independent of gut microbial dysbiosis. Interestingly, the expression of inflammatory genes and the activation of inflammatory pathways, including NF-kappaB, ERK, and STAT3 are significantly higher in Nod2(-/-) mouse colons during colitis and colorectal tumorigenesis, but not at homeostasis. Consistent with higher inflammation, there is greater proliferation of epithelial cells in hyperplastic regions of Nod2(-/-) colons. In vitro studies demonstrate that, while NOD2 activates the NF-kappaB and MAPK pathways in response to MDP, it inhibits TLR-mediated activation of NF-kappaB and MAPK. Notably, NOD2-mediated downregulation of NF-kappaB and MAPK is associated with the induction of IRF4. Taken together, NOD2 plays a critical role in the suppression of inflammation and tumorigenesis in the colon via downregulation of the TLR signaling pathways. |
