Articles: smad7-protein.
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Current drug metabolism · Jan 2016
ReviewSmad7 and its Potential as Therapeutic Target in Inflammatory Bowel Diseases.
The etiology of Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) in humans, is still unknown, but evidence suggests that genetic and environmental factors interact to promote an excessive immune response that leads to tissue damage. Defects in the counter-regulatory mechanisms are also supposed to make a major contribution to the amplification and maintenance of the IBD-related inflammatory response. One such a mechanism involves TGF-β1, a cytokine synthesized by both immune and non-immune cells in the gut, which is essential in the maintenance of immune homeostasis. In both CD and UC, active inflammation occurs in areas characterized by enhanced production of TGF-β1 and reduced ability of this cytokine to activate Smad-associated signaling and suppress inflammatory pathways. The defective TGF-β1 activity is due to elevated levels of Smad7, an intracellular protein that inhibits TGF-β1-associated Smad signaling. ⋯ Data indicate that, in IBD, high Smad7 contributes to sustain detrimental immune responses and knockdown of this molecule can help attenuate the ongoing mucosal inflammation in patients with such disorders.
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Genome-wide association studies (GWASs) and a number of case-control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study. A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. ⋯ Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian. Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.