Abstract Piezo1 is a nonselective cationic mechanosensitive channel, the overactivation of which is closely associated with the pathogenesis of various neurological disorders. Our previous study has demonstrated that the protein expression of Piezo1 was upregulated after chronic cerebral hypoperfusion (CCH) injury. Inhibiting Piezo1 could ameliorate CCH-induced cognitive dysfunction and blood–brain barrier (BBB) damage. Pericytes plays a crucial role in maintaining the structural and functional integrity of BBB, yet whether inhibition of Piezo1 has a direct protective effect on pericytes remains uncertain. To mimic ischemic and hypoxic conditions, primary pericytes were exposed to oxygen glucose deprivation/reoxygenation (OGD/R). In the present study, we aimed to investigate the effects of inhibiting Piezo1 on OGD/R-induced pericytes injury and its potential mechanisms. Our results demonstrated that OGD/R-induced injury of pericytes was significantly reversed by the selective Piezo1 inhibitor GsMTx4. Additionally, GsMTx4 treatment increased the expression of N-cadherin protein in pericytes and decreased the levels of inflammatory cytokines IL-1β, TNF-α, and IL-18. Furthermore, GsMTx4 reversed OGD/R-induced ultrastructural changes of cell morphology, and reduced the expression levels of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved-caspase1 and ASC. Notably, Nigericin, an NLRP3 inflammasome agonist, attenuated the aforementioned effects of GsMTx4 on pericytes. In conclusion, inhibiting Piezo1 effectively ameliorated OGD/R-induced pericytes injury, mitigated inflammatory responses and pyroptosis. Moreover, these cytoprotective effects were related to inhibition of the NLRP3 inflammasome activity. The present study provided a potential theoretical basis and therapeutic target for the treatment of CCH and other related cerebrovascular diseases.
(368913) et al. (Mon,) studied this question.