ArticleAnnals of the rheumatic diseases2011
HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus.
Article in Annals of the rheumatic diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 118 citations in OpenAlex.
- Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial.Annals of the rheumatic diseases · 2013Trial
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- Autophagy, NET formation, and inflammation crosstalk in thrombotic autoimmune diseases.Frontiers in immunology · 2026Review
- Role Transformation of HSPA8 to Heme-peroxidase After Binding Hemin to Catalyze Heme Polymerization.The protein journal · 2024Article
- Mechanisms of autophagy and their implications in dermatological disorders.Frontiers in immunology · 2024Review
- Phosphopeptides P140 cause oxidative burst responses of pulmonary macrophages in an imiquimod-induced lupus model.Molecular biomedicine · 2023Article
- The role of lysosomes in metabolic and autoimmune diseases.Nature reviews. Nephrology · 2023Review
- Immunological and translational key challenges in systemic lupus erythematosus: A symposium update.Journal of translational autoimmunity · 2023Article
- Article
- Therapeutic effects of peptide P140 in a mouse periodontitis model.Cellular and molecular life sciences : CMLS · 2022Article
- Associations between ATG16L1 gene polymorphism and antineutrophil cytoplasmic antibody-associated vasculitis in the Chinese Guangxi population: A case-control study.Journal of clinical laboratory analysis · 2022Article
- Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases.Biomolecules · 2022Review
- Review
- Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression.International journal of molecular sciences · 2022Review
- Cell type-specific mechanistic target of rapamycin-dependent distortion of autophagy pathways in lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- New Insights into the Mechanisms of Chaperon-Mediated Autophagy and Implications for Kidney Diseases.Cells · 2022Review
- P140 Peptide Leads to Clearance of Autoreactive Lymphocytes and Normalizes Immune Response in Lupus-Prone Mice.Frontiers in immunology · 2022Article
- HSPA8 Is a New Biomarker of Triple Negative Breast Cancer Related to Prognosis and Immune Infiltration.Disease markers · 2022Article
- Perturbed autophagy intervenes systemic lupus erythematosus by active ingredients of traditional Chinese medicine.Frontiers in pharmacology · 2022Review
- Targeting lysosomes in human disease: from basic research to clinical applications.Signal transduction and targeted therapy · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe P140 phosphopeptide issued from the spliceosomal U1-70K small nuclear ribonucleoprotein protein displays protective properties in MRL/lpr lupus-prone mice. It binds both major histocompatibility class II (MHCII) and HSC70/Hsp73 molecules. P140 peptide increases MRL/lpr peripheral blood lymphocyte apoptosis and decreases autoepitope recognition by T cells.
objectiveTo explore further the mode of action of P140 peptide on HSC70+ antigen-presenting cells.
methodsP140 biodistribution was monitored in real time using an imaging system and by fluorescence and electron microscopy. Fluorescence activated cell sorting and Western blotting experiments were used to evaluate the P140 effects on autophagic flux markers.
resultsP140 fluorescence accumulated especially in the lungs and spleen. P140 peptide reduced the number of peripheral and splenic T and B cells without affecting these cells in normal mice. Remaining MRL/lpr B cells responded normally to mitogens. P140 peptide decreased the expression levels of HSC70/Hsp73 chaperone and stable MHCII dimers, which are both increased in MRL/lpr splenic B cells. It impaired refolding properties of chaperone HSC70. In MRL/lpr B cells, it increased the accumulation of the autophagy markers p62/SQSTM1 and LC3-II, consistent with a downregulated lysosomal degradation during autophagic flux.
conclusionThe study results suggest that after P140 peptide binding to HSC70, the endogenous (auto)antigen processing might be greatly affected in MRL/lpr antigen-presenting B cells, leading to the observed decrease of autoreactive T-cell priming and signalling via a mechanism involving a lysosomal degradation pathway. This unexpected mechanism might explain the beneficial effect of P140 peptide in treated MRL/lpr mice.
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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 OpenQuestion graph.