Pathophysiological Role of Vimentin Intermediate Filaments in Lung Diseases

Abstract

Vimentin intermediate filaments, a type III intermediate filament, are among the most widely studied IFs and are found abundantly in mesenchymal cells. Vimentin intermediate filaments localize primarily in the cytoplasm but can also be found on the cell surface and extracellular space. The cytoplasmic vimentin is well-recognized for its role in providing mechanical strength and regulating cell migration, adhesion, and division. The post-translationally modified forms of Vimentin intermediate filaments have several implications in host-pathogen interactions, cancers, and non-malignant lung diseases. This review will analyze the role of vimentin beyond just the epithelial to mesenchymal transition (EMT) marker highlighting its role as a regulator of host-pathogen interactions and signaling pathways for the pathophysiology of various lung diseases. In addition, we will also examine the clinically relevant anti-vimentin compounds and antibodies that could potentially interfere with the pathogenic role of Vimentin intermediate filaments in lung disease.

Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 pathways

“…They are also considered markers for mesenchymal transitioning and myofibroblast formation. Fibronectin and vimentin are important for fibroblast migration, activation, enhanced inflammation through NLRP3, and epithelial-mesenchymal transition through activating the TGF-β1/Smad pathway 65 . BLM increased the level of these ECM proteins in the immune-stained lung sections, whereas VCN managed to dampen their expression.…”

“…The transition from fibroblasts and other mesenchymal cells to myofibroblasts (MFBs) is critical to developing and progressing pulmonary fibrosis 86 . Where TGF-β1 activates fibroblasts through Smad2/3 signaling transduction, which results in increased expression of ECM components (fibronectin and vimentin) that further participate in the proliferation, migration, and trans-differentiation of fibroblasts into myofibroblasts that express a high level of α-SMA 65 , VCN managed to reduce the expression of the fibrotic indices for ECM deposition and the signaling protein (Smad2/3) involved in the activation of fibroblasts and transitioning into ECM-producing myofibroblasts in MRC-5 induced with TGF-β1. VCN produced its effect probably due to either blocking the binding of TGF-β1 to its specific receptors (TGF-βRI and TGF-βRII) or inhibiting the production and activation of the intracellular signaling protein (Smad2/3) or other indirect signaling pathways, thus suppressing the TGF-β1/Smad2/3 pathway necessary for the activation, proliferation, and fibroblast transition into myofibroblast and halting further production of collagen and other components of ECM (vimentin, fibronectin, and α-SMA).…”

Vimentin expression correlates with immune checkpoint inhibitor efficacy in non–small cell lung cancer

“…Vimentin is a type III intermediate filament that plays roles related to the maintenance of cell migration, mechanical strength, division, and adhesion. [1][2][3] Vimentin is expressed in some mesenchymal cells, such as endothelial cells and fibroblasts, but is also frequently found in epithelial tumors. [4][5][6] It is believed that vimentin is involved in carcinogenesis through a variety of mechanisms.…”

Dual Affinity Nanoparticles for the Transport of Therapeutics from Carrier Cells to Target Cells under Physiological Flow Conditions

“…22,23 Additionally, it is an attractive target as it is only involved in endocytosis pathways in viral infections, making it a well-suited target for cell surface drug delivery (such as TRAIL therapies). 24 The dual affinity (DA) liposomes are functionalized with TRAIL, ES, and anti-CSV half antibodies on their surface.…”

“…As a proof of concept, cell surface vimentin (CSV) was chosen as the target protein due to the presence of vimentin on the cell surface of cancer cells along the EMT/MET axis, making it an attractive target for a nanoparticle-based drug delivery model for highly metastatic CTCs . It is selectively expressed on their surface and not on the surface of healthy cells. , Additionally, it is an attractive target as it is only involved in endocytosis pathways in viral infections, making it a well-suited target for cell surface drug delivery (such as TRAIL therapies) . The dual affinity (DA) liposomes are functionalized with TRAIL, ES, and anti-CSV half antibodies on their surface.…”