ArticleAnnals of translational medicine2021
Effect and mechanism of phospholipid scramblase 4 (PLSCR4) on lipopolysaccharide (LPS)-induced injury to human pulmonary microvascular endothelial cells.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis.Frontiers in physiology · 2024Pooled it
- Investigating the role of miR-192-5p as a diagnostic biomarker and the anti-inflammatory function in pediatric acute respiratory distress syndrome.BMC immunology · 2026Article
- USP7-Mediated ICAM1 Facilitates Lipopolysaccharide-Induced Human Pulmonary Microvascular Endothelial Cell Injury to Accelerate Pediatric Acute Respiratory Distress Syndrome.The clinical respiratory journal · 2025Article
- Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation.International journal of molecular sciences · 2022Article
- Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model.Bioengineered · 2022Article
- Role of Pyroptosis in Respiratory Diseases and its Therapeutic Potential.Journal of inflammation research · 2022Review
- The role of pyroptosis in endothelial dysfunction induced by diseases.Frontiers in immunology · 2022Review
- Article
- Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells.Experimental and therapeutic medicine · 2021Article
- The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review.Frontiers in immunology · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious experiments revealed phospholipid scramblase 4 (PLSCR4) mRNA to be significantly increased in a lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model of human pulmonary microvascular endothelial cells (HPMECs); however, the effect of PLSCR4 and its mechanism have not been reported to date. The PLSCR family is thought to mediate the transmembrane movement of phospholipids (PS), and has been found to be involved in pyroptosis through combing with gasdermin D (GSDMD). We therefore speculated that PLSCR4 may contribute to cell death via pyroptosis.
methodsTo investigate the effect and mechanism of PLSCR4 in ARDS, we constructed an in vitro model of LPS-induced ARDS in HPMECs transfected with PLSCR4 small interfering RNA (siRNA) or scramble siRNA (sc siRNA). After 4 h of LPS stimulation, western blotting, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), tracer flux assays, and fluorescence assays were used to study the relationship between PLSCR4 and pyroptosis with regards to their impact on ARDS. We also established an ARDS mouse model which was pretreated with a liquid complex of PLSCR4 siRNA/sc siRNA-lipofectamine 2000 through the fundus venous plexus. Finally, we used DNA pull-down and protein profiling to study the potential transcription factor of PLSCR4.
resultsIt was found that when the expression of PLSCR4 was elevated, the concentration of interleukin 1 beta (IL-1β) and IL-18 decreased, along with barrier damage (P<0.05). Furthermore, HPMEC injury was reduced with more distribution of PS and N-terminal cleavage product (GSDMD-NT) of GSDMD on the external side of cell membrane. However, the pyroptosis-relevant proteins of GSDMD and caspase-1 were not obviously changed (P<0.05); we further found that when PLSCR4 was depressed, the lung injury was aggravated in the mice. In the DNA pull-down assay, P62280 remarkably increased, which suggested that P62280 might be the transcription factor for PLSCR4.
conclusionsPLSCR4 alleviated pyroptosis by transporting PS to the outside of the membrane, blocking the formation of pyroptosis pores composed of GSDMD. Moreover, P62280 might be the transcription factor of PLSCR4. These insults may provide useful insights into the clinical treatment of ARDS.
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