Transcriptional and Phenotypic Characterization of Vimentin Knockout Mouse during Aging

Abstract

Vimentin is a type III intermediate filament (IF) that primarily found in mesenchymal cells and plays important roles in epithelial‐mesenchymal transition (EMT). IFs were originally thought to be a relatively static structure that mainly functioned as mechanical support. However, in the past decades, it has been shown that IF networks are highly dynamic structures and their roles have expanded from maintenance of cell shape and integrity to cellular migration, adhesion, and cancer metastasis. Vimentin knockout mouse was originally reported to have no overt phenotype, leading to the conclusion that vimentin IF represented an unnecessary cytoskeletal system. Interestingly, our group recently found that acute lung injury (ALI) is attenuated in mice lacking vimentin when challenged with either LPS, asbestos, or bleomycin. Moreover, these studies demonstrated vimentin to be a key player in the activation of the NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) inflammasome, an intracellular protein complex that is activated in response to stimuli such as bacterial and viral pathogens, including influenza A virus. In this study, we thoroughly characterize young and aged vimentin knockout mice behaviorally using battery of neurocognitive tests and show that there are age‐dependent changes in neuromuscular, neurocognitive, and metabolic lung functions distinctively from the wild type mice. We also use RNA sequencing as an unbiased approach to study transcriptional changes and identify a significant number of differentially expressed genes between the two groups in various cell types and with aging. Additionally, histological analyses from multiple organs of these mice also suggest a crucial role of vimentin in maintaining cellular structures and functions during aging. In conclusion, our data suggests that vimentin intermediate filament plays dynamic roles in multiple organ systems and during aging.Support or Funding InformationNHLBI R01 HL128194This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.