ArticleCell death and differentiation2016
Thrombospondin 1 protects pancreatic β-cells from lipotoxicity via the PERK-NRF2 pathway.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Endothelial IRE1α promotes thrombospondin-1 mRNA decay and supports metabolic stress adaptation of pancreatic islets.Nature communications · 2026Article
- Trophoblast cell response to periodontal pathogens unveils oxidative stress networks between periodontitis and pre-eclampsia: Mendelian randomization, transcriptomic analysis, and cellular experimental validation.European journal of medical research · 2025Article
- Restorative Effects of Synbiotics on Colonic Ultrastructure and Oxidative Stress in Dogs with Chronic Enteropathy.Antioxidants (Basel, Switzerland) · 2025Article
- The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.Journal of advanced research · 2025Article
- Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.Nature communications · 2025Article
- The role of endothelial cells in pancreatic islet development, transplantation and culture.Frontiers in cell and developmental biology · 2025Review
- Importance of unfolded protein response modulation on diabetes management: a systematic review.Journal of diabetes and metabolic disorders · 2024Review
- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- Gender-specific effects of oxidative balance score on the prevalence of diabetes in the US population from NHANES.Frontiers in endocrinology · 2023Article
- Gene Delivery of Manf to Beta-Cells of the Pancreatic Islets Protects NOD Mice from Type 1 Diabetes Development.Biomolecules · 2022Article
- Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing.iScience · 2022Article
- Thrombospondin 1 Promotes Endoplasmic Reticulum Stress and Apoptosis in HK-2 Cells by Upregulating ATF6-CHOP.Current medical science · 2022Article
- The parasite-derived peptide FhHDM-1 activates the PI3K/Akt pathway to prevent cytokine-induced apoptosis of β-cells.Journal of molecular medicine (Berlin, Germany) · 2021Article
- CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes.American journal of physiology. Cell physiology · 2021Review
- Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy.Nature communications · 2021Article
- Network-based analysis of key regulatory genes implicated in Type 2 Diabetes Mellitus and Recurrent Miscarriages in Turner Syndrome.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The failure of β-cells has a central role in the pathogenesis of type 2 diabetes, and the identification of novel approaches to improve functional β-cell mass is essential to prevent/revert the disease. Here we show a critical novel role for thrombospondin 1 (THBS1) in β-cell survival during lipotoxic stress in rat, mouse and human models. THBS1 acts from within the endoplasmic reticulum to activate PERK and NRF2 and induce a protective antioxidant defense response against palmitate. Prolonged palmitate exposure causes THBS1 degradation, oxidative stress, activation of JNK and upregulation of PUMA, culminating in β-cell death. These findings shed light on the mechanisms leading to β-cell failure during metabolic stress and point to THBS1 as an interesting therapeutic target to prevent oxidative stress in type 2 diabetes.
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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.