ArticleJCI insight2024
FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Nuclear m6A Methylase METTL3 Drives Production of ITGβ4E to Exacerbate Heart Failure via SRSF3-Mediated Alternative Splicing of ITGβ4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Post-translational modifications of integrins: molecular mechanisms and pathological implications.Cellular and molecular life sciences : CMLS · 2026Review
- FLRT2 promotes foam cell formation and atherosclerosis by inhibiting USP22-mediated ABCA1 deubiquitination.Acta pharmacologica Sinica · 2026Article
- Shared multicellular injury programs of acute and chronic kidney disease enable mechanistic patient stratification.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets.JHEP reports : innovation in hepatology · 2025Article
- Endothelium-specific sensing of mechanical signals drives epidermal aging through coordinating retinoid metabolism.Theranostics · 2025Article
- Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.Nature communications · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The roles of fibronectin leucine-rich transmembrane protein 2 (FLRT2) in physiological and pathological processes are not well known. Here, we identify a potentially novel function of FLRT2 in preventing endothelial cell senescence and vascular aging. We found that FLRT2 expression was lower in cultured senescent endothelial cells as well as in aged rat and human vascular tissues. FLRT2 mediated endothelial cell senescence via the mTOR complex 2, AKT, and p53 signaling pathway in human endothelial cells. We uncovered that FLRT2 directly associated with integrin subunit beta 4 (ITGB4) and thereby promoted ITGB4 phosphorylation, while inhibition of ITGB4 substantially mitigated the induction of senescence triggered by FLRT2 depletion. Importantly, FLRT2 silencing in mice promoted vascular aging, and overexpression of FLRT2 rescued a premature vascular aging phenotype. Therefore, we propose that FLRT2 could be targeted therapeutically to prevent senescence-associated vascular aging.
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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 OpenQuestion graph.