Role of Nephronectin in Pathophysiology of Silicosis

Abstract

Silicosis is a typical form of pneumoconiosis and is characterized as a type of lung fibrosis. Silica particles are captured and recognized upon by alveolar macrophages via the macrophage receptor with collagenous structure (MARCO) scavenger receptor, and thereafter the inflammasome is activated. Thereafter, various chemokines/cytokines play their roles to eventually form fibrosis. Additionally, silica particles chronically activate T helper cells which sets the background for the formation of silicosis-associated autoimmune disturbances. The occurrence and progression of lung fibrosis, the extracellular matrix-related molecules such as integrins and their ligands including fibronectin, vitronectin, laminin, and collagens, all play important roles. Here, the roles of these molecules in silicosis-related lung fibrosis are reviewed from the literature. Additionally, the measurement of serum nephronectin (Npnt), a new member of the integrin family of ligands, is discussed, together with investigations attempting to delineate the role of Npnt in silica-induced lung fibrosis. Serum Npnt was found to be higher in silicosis patients compared to healthy volunteers and seems to play a role in the progression of fibrosis with other cytokines. Therefore, serum Npnt levels may be employed as a suitable marker to monitor the progression of fibrosis in silicosis patients.

Multisystem Amyloidosis in a Coal Miner with Silicosis: Is Exposure to Silica Dust a Cause of Amyloid Deposition?

“…Silica particles are known to be an adjuvant factor; the substance activates the immunologic system [ 16 ]. Macrophages play a central role in this process.…”

“…The exact mechanism of how advanced silicosis causes monoclonal immunoglobulin production is not entirely known; however, experimental data has shown that silica may have played an important role in lymphocyte B clone generation and immunoglobulin production [ 18 ]. The chronic inflammatory state observed in patients with silicosis probably plays a key role in stimulating B cells as well [ 16 ]. Additionally, the specific tissue deposition pattern typical for patients with end-stage renal disease may play a role in transforming amyloid protein into an insoluble fibril structure [ 19 ].…”

Characterization of a COPD-Associated NPNT Functional Splicing Genetic Variant in Human Lung Tissue via Long-Read Sequencing

“…It was first identified in the context of the search for a novel ligand for integrin α8β1 22,23 and was shown to be necessary for normal kidney development in murine models 24 . NPNT has also been linked to osteoblast differentiation and bone remodeling 25 , invasiveness of breast cancer 26 , and pulmonary silicosis 27 . Full-length NPNT protein includes five epidermal growth factor (EGF)-like functional domains followed by a meprin, A-5 protein, receptor protein-tyrosine phosphatase mu (MAM), and an Arg-Gly-Asp (RGD) integrin-binding domain.…”

The Mechanism and Effect of Autophagy, Apoptosis, and Pyroptosis on the Progression of Silicosis

“…The current widely accepted silicosis pathogenesis is as follows: (1) Silica is identified and then phagocytosed by the alveolar macrophage (AM) via the scavenger receptor, which is the first critical defensive line for silica invasion [ 5 , 6 ]. Silicosis is developed through a vicious circle.…”