Reelin protects from colon pathology by maintaining the intestinal barrier integrity and repressing tumorigenic genes

摘要: We previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of current study was determine whether reelin protects from colorectal cancer and how defends colon pathology. In wild-type mice lacking (reeler mice) we have analysed the: i) epithelium cell renewal processes, ii) morphology, iii) Sox9, Cdx2, Smad5, Cyclin D1, IL-6 IFNγ mRNA abundance DSS-treated untreated mice, iv) development azoxymethane/DSS-induced cancer, using histological real time-PCR methodologies. reeler mutation increases colitis-associated tumorigenesis, with increased tumours number size. It also impairs intestinal barrier because it proliferation, differentiation apoptosis; decreases maturation goblet cells, expands intercellular space desmosomes. impairment might explain pathology exhibited by is at least mediated down-regulation Sox9 Cdx2. response DSS-colitis, IL-6, Smad5 D1 IFNγ, conditions result tumorigenesis found mice. conclusion, results highlight a maintaining epithelial homeostasis providing resistance against