Gender- and Age-Based Characterization and Comparison of the Murine Primary Peritoneal Mesothelial Cell Proteome

Abstract

Organs in the abdominal cavity are covered by a peritoneal membrane, which is comprised of a monolayer of mesothelial cells (MC). Diseases involving the peritoneal membrane include peritonitis, primary cancer (mesothelioma), and metastatic cancers (ovarian, pancreatic, colorectal). These diseases have gender- and/or age-related pathologies; however, the impact of gender and age on the peritoneal MC is not well evaluated. To address this, we identified and characterized gender- and age-related differences in the proteomes of murine primary peritoneal MC. Primary peritoneal MC were isolated from young female (FY) or male (MY) mice (3-6 months) and aged female (FA) or male (MA) mice (20-23 months), lysed, trypsin digested using S-Traps, then subjected to bottom-up proteomics using an LC-Orbitrap mass spectrometer. In each cohort, we identified >1000 protein groups. Proteins were categorized using Gene Ontology and pairwise comparisons between gender and age cohorts were conducted. This study establishes baseline information for studies on peritoneal MC in health and disease at two physiologic age/gender points. Segregation of the data by gender and age could reveal novel factors to specific disease states involving the peritoneum. [This in vitro primary cell model has utility for future studies on the interaction between the mesothelium and foreign materials.] SUMMARY STATEMENTMany diseases initiate from or involve peritoneal mesothelial cells including peritonitis, primary cancer (mesothelioma) and metastatic cancers. Progression of these diseases is influenced by many host factors including gender and age; however, the influence of these factors on the peritoneal mesothelial cell proteome has not been evaluated. This study provides novel information and identifies proteins exclusive to both male and female young and aged cohorts. Given the importance of the peritoneal mesothelial cell in abdominal homeostasis, and the impact of gender and age on disease progression, these data will be key for future studies examining mesothelium in both health and disease.