ArticleDiabetologia2018
MANF protects human pancreatic beta cells against stress-induced cell death.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- The role of mesencephalic astrocyte-derived neurotrophic factor in digestive diseases.Annals of medicine · 2026Review
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Investigation of MANF regulation of glioma stemness via STAT3/TGF-β/SMAD4/p38 pathway based on pan-cancer analysis.Translational oncology · 2025Article
- Identification and validation of the pivotal role of MANF gene in pancreatic β-cell aging using bioinformatics.Biochemistry and biophysics reports · 2025Article
- Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells.Stem cell reports · 2025Article
- Oral colon-targeted delivery of recombinant human MANF for alleviation of ulcerative colitis.International journal of pharmaceutics: X · 2025Article
- Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.Molecular biology reports · 2024Review
- E3 Ubiquitin Ligase Ring Finger Protein 2 Alleviates Cerebral Ischemia-Reperfusion Injury by Stabilizing Mesencephalic Astrocyte-Derived Neurotrophic Factor Through Monoubiquitination.CNS neuroscience & therapeutics · 2024Article
- The DoGA consortium expression atlas of promoters and genes in 100 canine tissues.Nature communications · 2024Article
- Increased expression of mesencephalic astrocyte-derived neurotrophic factor (MANF) contributes to synapse loss in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- MANF serves as a novel hepatocyte factor to promote liver regeneration after 2/3 partial hepatectomy via doubly targeting Wnt/β-catenin signaling.Cell death & disease · 2024Article
- Dual role of neuroplastin in pancreatic β cells: Regulating insulin secretion and promoting islet inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Machine learning and 4D-LFQ quantitative proteomic analysis explore the molecular mechanism of kidney stone formation.Heliyon · 2024Article
- Navigating the Landscape of MANF Research: A Scientometric Journey with CiteSpace Analysis.Cellular and molecular neurobiology · 2023Review
- Upregulation of mesencephalic astrocyte-derived neurotrophic factor (MANF) expression offers protection against alcohol neurotoxicity.Journal of neurochemistry · 2023Article
- CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson's disease.Frontiers in psychiatry · 2023Review
- Characterization of the functional and transcriptomic effects of pro-inflammatory cytokines on human EndoC-βH5 beta cells.Frontiers in endocrinology · 2023Article
- Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 4 countries.
Funding
Abstract
aims/hypothesisThere is a great need to identify factors that could protect pancreatic beta cells against apoptosis or stimulate their replication and thus prevent or reverse the development of diabetes. One potential candidate is mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum (ER) stress inducible protein. Manf knockout mice used as a model of diabetes develop the condition because of increased apoptosis and reduced proliferation of beta cells, apparently related to ER stress. Given this novel association between MANF and beta cell death, we studied the potential of MANF to protect human beta cells against experimentally induced ER stress.
methodsPrimary human islets were challenged with proinflammatory cytokines, with or without MANF. Cell viability was analysed and global transcriptomic analysis performed. Results were further validated using the human beta cell line EndoC-βH1.
resultsThere was increased expression and secretion of MANF in human beta cells in response to cytokines. Addition of recombinant human MANF reduced cytokine-induced cell death by 38% in human islets (p < 0.05). MANF knockdown in EndoC-βH1 cells led to increased ER stress after cytokine challenge. Mechanistic studies showed that the protective effect of MANF was associated with repression of the NF-κB signalling pathway and amelioration of ER stress. MANF also increased the proliferation of primary human beta cells twofold when TGF-β signalling was inhibited (p < 0.01). CONCLUSIONS/
interpretationOur studies show that exogenous MANF protein can provide protection to human beta cells against death induced by inflammatory stress. The antiapoptotic and mitogenic properties of MANF make it a potential therapeutic agent for beta cell protection.
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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.