Inflammation was accompanied by a nuclear accumulation of p53 and changes in cell identity/properties as manifested particularly by the presence of UACL in IBD. We provided a mechanistic link between p53 and LM by demonstrating that p53 transactivates LAMA1 expression through promoter binding. We further showed an attenuated response to DSS-induced inflammation in transgenic mice overexpressing either the LMa1 or LM a5 chain. Yet, overexpression of the same LM molecules could participate in the progression of IBD into colitis-associated cancer upon acquisition of oncogenic mutations as exemplified by AOM/DSS or chronic DSS treated transgenic mice. Our data point to the distinct, sometimes opposing properties of LM, reinforcing their described potential dual functions. Here we showed that in upon inflammation, both LMa1 and LMa5 chains are overexpressed using human IBD and murine colitis specimens. Furthermore we demonstrated in transgenic mice that both LM attenuate DSS-induced inflammation as shown by a reduced inflammatory score and a decreased expression of pro-inflammatory cytokines. These data suggest that a1/a5 chaincontaining LM potentially play a role in the IBD disease by limiting colitis. At present time, it was not possible to determine the precise expressed LM isoform, as nobody has managed so far to isolate such thin in vivo BM. Yet, the functionality of the LM isoform is known to be mainly mediated by the LMa chain though interaction with cell membrane receptors. Here we provided arguments showing that LMa1 and LMa5 act probably via two distinct mechanisms. We first examined a potential involvement of NF-kB because of its documented role in intestinal inflammation. We provided evidence that LM-511 is LY294002 PI3K inhibitor indeed able to attenuate the TNFa-stimulated expression of the NF-kB reporter. Since LM are constituents of BM which serve as physical and chemical barriers in epithelial tissues it is also possible that their increased abundance in IBD strengthens the BM barrier. Indeed, a cell-derived matrix that contains the LMa1 chain showed an increased stiffness in vitro. Altered mechanical properties of LMa1 rich-BM may contribute to protection from inflammation. This hypothesis could be verified in the future owing to the recently developed technology of AFM on isolated BM. Reinforcing BM stability/organization could be a promising therapeutic approach in the early phases of IBD. This might be feasible as a LM substitution “therapy” was already applied to the LMa2 chain-deficient mice where transgenic expression or systemic administration of LM-111 reduced muscular dystrophy. Linked to IBD, reintroduction of colon organoids into superficially damaged mouse colon is now feasible. LM could also play a role in tissue restitution as there is some evidence from in vitro studies that they promote “wound” closure of disrupted epithelial cell monolayers which is important in tissue rebuilding.