ArticleCell death discovery2025
Endothelial mechanosensitive transcription factor BHLHE40 induced by Piezo1 suppresses endothelial ferroptosis and inflammation via SLC7A11.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
3 citing papers in PubMed.
- Linking Gut Microbiota, Mitochondrial Redox Dysfunction, and Ferroptosis in Cardiometabolic Diseases: A Narrative Review of Mechanistic Evidence and Redox-Targeted Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Calcium homeostasis imbalance in sepsis: molecular mechanisms and therapeutic perspectives.Frontiers in medicine · 2026Review
- Exercise-altered fluid shear stress regulates vascular endothelial inflammation via Piezo1.Frontiers in physiology · 2026Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Endothelial dysfunction-driven vascular inflammation underlies sepsis and atherosclerosis. Piezo1 serves as a central mediator for endothelial mechanotransduction and inflammatory homeostasis. Nevertheless, the transcriptional pathways linking mechanical sensing to anti-inflammatory protection and the exact composition of its downstream signaling cascade remain incompletely resolved. Here, we identify BHLHE40 as an endothelial mechanosensitive transcription factor induced by Piezo1 that coordinates ferroptosis resistance and inflammation suppression. Mechanistically, shear stress activates Piezo1, triggering Ca²⁺ influx and calcineurin-dependent NFAT2 nuclear translocation. NFAT2 recruits HDAC1 to form a transcriptional complex that directly drives BHLHE40 expression. BHLHE40 then binds the SLC7A11 promoter, upregulating this cystine transporter to inhibit ferroptosis. Rescued mitochondrial integrity, reduced ROS, and reversed lipid peroxidation demonstrated this phenomenon. Crucially, mice with endothelial-specific BHLHE40 overexpression attenuate LPS-induced lung vascular leakage, neutrophil infiltration, and pro-inflammatory cytokine release. Our work establishes the Piezo1/Ca²⁺/calcineurin/NFAT2-HDAC1/BHLHE40/SLC7A11 axis as a master mechanotransduction pathway that transcriptionally maintains endothelial homeostasis.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.