Roles of Piezo1 in chronic inflammatory diseases and prospects for drug treatment (Review)

Abstract

The human body is chronically stimulated by various mechanical forces and the body cells can sense harmful stimuli through mechanotransduction to induce chronic inflammation. Piezo type mechanosensitive ion channel component 1 (Piezo1), a novel transmembrane mechanosensitive cation channel, is widely expressed in inflammatory cells, such as neutrophils, macrophages and endothelial cells, as well as in non‑inflammatory cells, such as osteoblasts, osteoclasts and periodontal cells. A growing number of studies have demonstrated that Piezo1 senses changes in environmental mechanical forces, regulates cellular functions and influences the development and regression of chronic inflammation. The present study summarized the roles of Piezo1 and its possible mechanisms in some common chronic inflammatory diseases and evaluated the potential application of drugs that modulate its activity, so as to prove that Piezo1 is likely to become a new target for the treatment of inflammatory diseases.15.

Keywords: Piezo type mechanosensitive ion channel component 1; chronic inflammation; mechanotransduction; periodontitis; pharmacotherapy.

Figure 1.

The structure of Piezo1. (A) The top view of the three propeller-like structural domains of Piezo1. (B) Each blade-like propeller of Piezo1 contains a unique 38 transmembrane α-helices: The N-terminal blade in the mechanosensory module, the C-terminal ion-conducting pore module and the transactivation module consisting of the anchor and the beam. L1342 and L1345 acts as fulcrums to form a lever-like structure that ensures selective cation penetration. (C) Mechanism of the activation of Piezo1 by extracellular mechanical forces. Piezo1, Piezo type mechanosensitive ion channel component 1; THUs, transmembrane helical units; IH, inner helix; OH, outer helix; CTD, C-terminal intracellular structural domain; CED, C-terminal extracellular structural domains.

Figure 2.

Role of Piezo1 in chronic inflammatory diseases. Piezo1, Piezo type mechanosensitive ion channel component 1; VILI, ventilator-associated lung injury; ARDS, acute respiratory distress syndrome.