Crohn’s Disease (CD) is a chronic and relapsing condition that affects millions of people worldwide. The defining feature of CD is the presence of mucosal wounds (ulcers), which result from complex interactions among microbiota, immune cells, and gut epithelial cells. Achieving healing of these mucosal wounds is associated with better health outcomes, but this occurs in fewer than half of the cases. Therefore, it is crucial to identify tissue-specific targets that promote mucosal healing, enhance outcomes, and minimize adverse effects.
Long non-coding RNAs (lncRNAs) represent a large and diverse class of non-protein-coding genes that exhibit tissue-specific expression. They have been shown to play key regulatory roles in cellular functions, particularly in regulating immunity and inflammation. In our research, we identified several altered lncRNAs associated with CD in both epithelial and immune cells. To investigate their mechanisms of action, we developed novel model systems to explore their functions in relation to microbiota interactions. Our findings revealed that various lncRNAs regulate crucial epithelial functions vital for maintaining epithelial barrier integrity, which becomes altered during gut inflammation. For instance, HNF1A-AS1 is involved in regulating epithelial renewal, GATA6-AS1 affects metabolic and mitochondrial functions, and a reduction in LHFPL3-AS2 impacts epithelial polarity. We published these discoveries in several peer-reviewed scientific journals (
https://www.habermanlab.sites.tau.ac.il/(se abrirá en una nueva ventana)). Because CD lncRNAs demonstrate high tissue specificity, they represent promising targets for potential future interventions with a lower risk of adverse effects.
