ArticlePloS one2025
Piezo1 regulates autophagy in HT22 hippocampal neurons through the Ca2+/Calpain and Calcineurin/TFEB signaling pathways.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- NF-κB-Dependent Transcriptional Regulation of Piezo1 Mediates Bacterial Clearance on Infected Lung Stiffness.American journal of respiratory cell and molecular biology · 2026Article
- Metal Ion-Mediated Regulation of Cell Fate: A Novel Strategy for Synergy with Radiotherapy and Immunotherapy.Cancers · 2026Review
- Review
- Yoda1-activated Piezo1 enhances mitophagy in human gingival fibroblasts to promote maxillofacial wound repair.Frontiers in pharmacology · 2026Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the functional and molecular mechanisms by which Piezo1regulates HT-22 hippocampal neuronal autophagy, and to explore whether Piezo1 regulates hippocampal neuronal autophagy via the Ca2+/Calpain, CaMKKβ, or Calcineurin pathways.
methodsThe impacts of Piezo1 inhibition, activation and gene knockdown on the autophagy of HT22 neurons was investigated by Western blotting, PCR and immunofluorescence. The changes of intracellular calcium (Ca2+) concentration were also observed. To pinpoint the specific downstream Ca2+ signaling pathway by which Piezo1 modulates autophagy, the calcium chelator BAPTA-AM, the Calpain inhibitor PD151746, and the CaMKKβ inhibitor STO609 were employed either alone or in combination.
resultsEnhanced autophagy was observed when Piezo1 was activated using the agonist Yoda1, manifesting as increased release of autophagic vacuoles, enhanced LC3 II/LC3 I ratio, decreased p62 protein level, and elevated nuclear translocation and expression of the TFEB protein. ATG7 knockdown by ATG7 shRNA mitigated the effects of Yoda1 on LC3 II/LC3 I ratio and p62 protein levels. The Piezo1 inhibitor GsMTx4 partially reversed the autophagy caused by starvation in HT22 neurons while Yoda1 still activated autophagy in the presence of BDNF. Following Piezo1 knockdown, neuronal autophagy was decreased. Piezo1-induced autophagy was accompanied with an increased cytoplasmic concentration of Ca2+. The calcium chelator BAPTA-AM partly reversed Piezo1 activation-induced autophagy, which was also mitigated by blocking calcineurin/TFEB signaling or Calpain signaling.
conclusionPiezo1 modulates the autophagy of HT-22 neurons by activating Ca2+/Calpain and Calcineurin/TFEB pathways.
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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.