Ninjurin 2 Modulates Tumorigenesis, Inflammation, and Metabolism via Pyroptosis

Am J Pathol. 2024 Feb 5:S0002-9440(24)00044-0. doi: 10.1016/j.ajpath.2024.01.013. Online ahead of print.ABSTRACTThe nerve injury induced protein 2 (NINJ2) belongs to a family of homophilic adhesion molecules and was initially found to be involved in nerve regeneration. However, the role of NINJ2 in other cellular process are not well studied. Here, by generating a Ninj2-deficient mouse model, we showed that mice deficient in Ninj2 have a short lifespan and are prone to spontaneous tumors, systemic inflammation and metabolic defects. To better understand the metabolic traits that contributes to these phenotypes, we performed comprehensive carbohydrate and lipid metabolic analyses. Carbohydrate metabolic analyses showed that NINJ2-deficiency led to defects in monosaccharide metabolism along with accumulation of multiple disaccharides and sugar alcohols. Lipidomic analyses showed that Ninj2 deficiency altered patterns of several lipids, including triglycerides, phospholipids and ceramides. To identify a cellular process that associated with these metabolic defects, we examined the role of NINJ2 in pyroptosis, a programmed cell death that links cancer, inflammation and metabolic disorders. We found that loss of NINJ2 promotes pyroptosis by activating the NLRP3 inflammasome. Taken together, these data reveal a critical role of NINJ2 in tumorigenesis, inflammatory response, and metabolism via pyroptosis.PMID:38325550 | DOI:10.1016/j.ajpath.2024.01.013
Source: Am J Pathol - Category: Pathology Authors: Source Type: research