The Role of Vimentin in Tissue Repair and Cell Growth

Microfilaments, microtubules, and intermediate filaments serve as the
cytoskeleton of the cell and form a complex network by interacting with
cytoskeleton-associated proteins. The cytoskeleton provides a framework for
the cell and regulates different cellular functions. Intermediate filaments form a
large family of proteins, which are classified into different groups based on their
structure and tissue expression pattern. Epithelial cells undergo epithelial mesenchymal transitions (EMT) during embryonic development, wound healing,
cancer, and fibrosis, to become proliferative, and migratory in nature. Vimentin
is a well-known EMT marker, but its role in EMT is not well characterized. This
thesis work investigated the role of vimentin in EMT during the wound healing
process, cell growth, and autoimmunity. In Vim-/- mice, delayed wound healing
due to defects in EMT signaling, keratinocyte cell migration, fibroblast cell
proliferation, and collagen deposition. Fibroblasts play an essential role in
normal development and wound healing. We observed that a lack of vimentin
resulted in reduced fibroblast cell size and due to deficient mTOR signaling.
Vimentin affected mTOR signaling by modulating Rag GTPase activity,
consequently regulating cell size and autophagy. We also found that vimentin
expression was increased in regulatory Treg cells, which control autoimmune
response, and this increase in expression was mediated through TGF-β1. This
thesis work provides evidence for the new roles of vimentin in tissue repair and
cellular growth.