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

Our plain-English summary of Gender- and Age-Based Characterization and Comparison of the Murine Primary Peritoneal Mesothelial Cell Proteome, by Z. Wang, Y. Liu, R. Safavisohi, et al (bioRxiv, 2024).

The study

• Authors: Z. Wang, Y. Liu, R. Safavisohi, M. Asem, D.D. Hu, M.S. Stack, M.M. Champion
• Journal: bioRxiv
• Published: 2024
• Read it: PubMed · Publisher · Free full text

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.].

In plain English

This laboratory study, posted as a preprint, compared proteins in mesothelial cells, which line the abdomen, from healthy mice. Cells came from 6 C57Bl/6 mice per group: young females, young males (3-6 months old), aged females and aged males (20-23 months old). The mice were untreated, and asbestos was not tested. Each mouse's cells were cultured separately, and their protein extracts were then pooled by group and analyzed by mass spectrometry. In all, 3,697 proteins and 1,215 protein groups were identified. Each group had proteins not found in the others, from 58 in young females to 423 in young males. Male and female cells differed in protein translation and peptide metabolism pathways, and young and aged cells differed in metabolic processes. Vimentin was higher in male than female cells at each age. The authors concluded the study provides baseline information for future research. They suggested the cultures could later be used to study interactions with foreign materials such as asbestos fibers. They noted three limits: the analyzed samples lacked extracellular matrix and secreted proteins, the collagen coating did not fully mimic the matrix in live animals, and fibroblasts and immune cells were absent.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (animal-derived cell culture) study comparing the protein content (proteomics) of primary mesothelial cells. Cells from each mouse were cultured separately. Lysates were then pooled within each of 4 groups and analyzed in technical triplicate, for 12 analyses in total.
• Who was studied: Primary peritoneal mesothelial cells from C57Bl/6 mice, 6 mice per cohort. The four cohorts were young females, young males, aged females and aged males. Young mice were 3-6 months old and aged mice were 20-23 months old. The work was done at the University of Notre Dame.
• Exposure: None. The mice received no treatments. The groups were compared only by sex and age, and no asbestos or other fiber exposure was studied.
• Main results:
  • Across all four cohorts, 3,697 proteins and 1,215 protein groups were identified.
  • Proteins and protein groups identified per cohort: aged female 2,721 and 899; young female 1,982 and 662; aged male 2,484 and 816; young male 2,364 and 805.
  • Proteins unique to each cohort: aged female 379 (150 protein groups); young female 58 (17); aged male 202 (66); young male 423 (137).
  • All cell nuclei in the cultures stained positive for both cytokeratin 18 and vimentin. The authors took this as showing the cultures lacked contaminating macrophages or fibroblasts.
  • Male and female mesothelial cells differed in protein translation and peptide metabolism pathways.
  • Aged and young mesothelial cells had distinct metabolic processes.
  • Vimentin was up regulated in aged male cells compared with aged female cells, and in young male cells compared with young female cells.
  • Cells from young mice survived longer in culture than cells from old mice: more than 1 month versus about 3 weeks. The authors did not show these data.
  • The authors stated the cultures are an in vitro model that could be used to examine how host sex and age affect interactions between the mesothelium and foreign materials such as asbestos fibers. This was not tested in this study.
• The authors' conclusion: The authors concluded that the study gives baseline information for future studies of peritoneal mesothelial cells in health and disease, at two age points.
• Limitations the authors state:
  • The samples analyzed lacked extracellular matrix and secreted proteins.
  • The collagen coating on the culture dishes does not fully mimic the more complex collagen matrix in live animals.
  • Fibroblasts and immune cells, which could affect the mesothelial cell proteome in living animals, were not part of the culture system.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mesothelioma, Peritoneum, Mesothelium.

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