Impact of Vimentin on Regulation of Cell Signaling and Matrix Remodeling

Abstract

Vimentin expression contributes to cellular mechanoprotection and is a widely recognized marker of fibroblasts and of epithelial-mesenchymal transition. But it is not understood how vimentin affects signaling that controls cell migration and extracellular matrix (ECM) remodeling. Recent data indicate that vimentin controls collagen deposition and ECM structure by regulating contractile force application to the ECM and through post-transcriptional regulation of ECM related genes. Binding of cells to the ECM promotes the association of vimentin with cytoplasmic domains of adhesion receptors such as integrins. After initial adhesion, cell-generated, myosin-dependent forces and signals that impact vimentin structure can affect cell migration. Post-translational modifications of vimentin determine its adaptor functions, including binding to cell adhesion proteins like paxillin and talin. Accordingly, vimentin regulates the growth, maturation and adhesive strength of integrin-dependent adhesions, which enables cells to tune their attachment to collagen, regulate the formation of cell extensions and control cell migration through connective tissues. Thus, vimentin tunes signaling cascades that regulate cell migration and ECM remodeling. Here we consider how specific properties of vimentin serve to control cell attachment to the underlying ECM and to regulate mesenchymal cell migration and remodeling of the ECM by resident fibroblasts.

The evolution of vimentin and desmin in Pectoralis major muscles of broiler chickens supports their essential role in muscle regeneration

“…The presence of degenerating/necrotic fibers, indeed, induces the activation of a satellite cell (SC)-mediated regeneration process whose first evidence at molecular and histological levels was observed in FG as early as two- and 3 weeks post-hatch, respectively ( Papah et al, 2017 , 2018 ; Sihvo et al, 2017 ). Intriguingly, this time course seems to perfectly match the findings achieved in the present study and support the hypothesis of a relevant role of VIM in muscle regeneration ( Ostrowska-Podhorodecka et al, 2022 ) which, in its turn, contributes to explain the absence of differences at the protein level between FG and MG birds at the beginning of the growing period. This initial similarity may be partially due to the response time needed to induce the development of the first regenerative processes to counteract myofiber degeneration and necrosis.…”

“…As previously reported, the VIM long-isoform differs from the common sequence by having a longer promoter and exon one regions ( Soglia et al, 2020 ). Interestingly, in humans these regions of VIM gene were recently demonstrated to bind proteins playing important roles in the transcription regulation of other genes and proteins implicated in protein synthesis (e.g., the eukaryotic elongation factor-1 complex; eEF-1), cell migration and extracellular matrix remodeling ( Al-Maghrebi et al, 2002 ; Pisani et al, 2016 ; Ostrowska-Podhorodecka et al, 2022 ). Therefore, dissimilarities between the two VIM sequences at the promoter level might suggest differences in regulating protein synthesis.…”

“…As mentioned above, the VIM gene may regulate extracellular matrix remodeling through post-transcriptional regulatory pathways concerning collagen synthesis ( Ostrowska-Podhorodecka et al, 2022 ) and fibroblast proliferation ( Danielsson et al, 2018 ). Differences in the expression level of VIM between FG and MG birds have been detected since the early stages of growth.…”

Photo-Crosslinked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Dural Substitute to Prevent Post-Surgical Adhesion

“…Vimentin is a widely recognized phenotypic marker for identifying fibroblasts [ 58 ], while recent studies indicate its key role in adhesion is by regulating integrin functions [ 59 ]. By contributing to the mechanical stabilization of cell structure, the expression of vimentin is crucial for effective tissue regeneration and wound healing [ 60 ]. It also helps to control the assembly of cell adhesions and migration through collagen matrices, while higher vimentin expression is associated with enhanced cell adhesion to the extracellular matrix and collagen deposition [ 61 ].…”

Transcriptome analysis reveals vimentin-induced downregulation of cell-cell associations augments cancer cell migration

“…It protects differentiating stem cells from stress by forming a cage around stress granules [16]. Vimentin delivers extracellular cues intracellularly by ECM remodelling via two mechanisms: rst, stabilising type 1 collagen mRNA, thereby synthesising more collagen 1 [17], and by modulating attachment of the cell to ECM [18]. It is involved in assembly of focal adhesions (FA)short squiggles of vimentin localise at nascent FA while lamentous vimentin is associated with mature FAs [19].…”