Long Noncoding RNA MIAT Regulates Hyperosmotic Stress-Induced Corneal Epithelial Cell Injury via Inhibiting the Caspase-1-Dependent Pyroptosis and Apoptosis in Dry Eye Disease

Abstract

Purpose The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs). Methods HCECs were cultured in 70–120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed. Results HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs. Conclusion The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.

IL-1β induced down-regulation of miR-146a-5p promoted pyroptosis and apoptosis of corneal epithelial cell in dry eye disease through targeting STAT3

“…There were many researches demonstrated that IL-1β was up-regulated in DED patients [9,27,28]. In addition to pyroptosis, caspase-1 is also involved in apoptosis in inflammatory situations [29]. Our results showed that IL-1β was highly expressed in DED model hCECs, and IL-1β silencing inhibited the thermal degeneration of DED model hCECs (Fig.…”

Dopamine Receptor 1 Treatment Promotes Epithelial Repair of Corneal Injury by Inhibiting NOD-Like Receptor Protein 3–Associated Inflammation

“…This, in turn, hampers the process of wound healing in traumatized ocular tissues. 18 , 19 Prior investigations into the interplay between DRD1 and inflammation have revealed that DRD1 functions as an anti-inflammatory agent by impeding activation of the NLRP3 inflammasome and the subsequent release of inflammatory cytokines, including caspase-1 and IL-1β. 6 Recent studies have elucidated the anti-inflammatory effects of DRD1 in conditions such as cerebral hemorrhage, acute kidney injury, and cardiac injury.…”

Research Progress of Pyroptosis in Ophthalmic Diseases

“…This provides a new mechanism for dexamethasone as an anti-inflammatory drug in dry eye. Long noncoding RNAMIAT has also been reported to regulate corneal epithelial cell damage induced by hyperosmotic stress by inhibiting Caspase-1-dependent corneal epithelial cell pyroptosis [24].…”