ArticleProceedings of the National Academy of Sciences of the United States of America2014
M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers.
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Who cites it
186 citing papers in PubMed, 317 citations in OpenAlex.
- Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.Islets · 2026Article
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.The Journal of clinical investigation · 2026Article
- The role of non-coding RNAs derived from macrophage exosomes in cardiovascular diseases.The Journal of physiology · 2026Review
- Genetic recording of pancreatic beta cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
- Spatiotemporal Heterogeneity of Macrophages in Acute Pancreatitis: From Inflammatory Initiators to Repair Coordinators and Targeted Therapeutics.Mediators of inflammation · 2026Review
- Targeting macrophage metabolism: mechanisms, cellular crosstalk and implications in obesity-associated metabolic diseases.Frontiers in immunology · 2026Review
- Mechanisms and therapeutic strategies for immunotherapy resistance in gastric cancer.Cancer cell international · 2025Review
- tRNA-Derived Small RNA Accelerates Tumorigenesis through Crosstalk with Tumor-Associated Macrophages, and Downregulation with Cell Membrane-Modified Polymer Nanoparticles Enables Treatment Response.ACS applied materials & interfaces · 2025Article
- M2-like macrophages derived from THP-1 cells promote myofibroblast differentiation of synovial fibroblasts in association with the TGF-β1/SMAD2/3 signaling pathway.Scientific reports · 2025Article
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Transcriptomic characterization of human pancreatic CD206- and CD206 + macrophages.Scientific reports · 2025Article
- Bioengineering Platelets Presenting PD-L1, Galectin-9 and BTLA to Ameliorate Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Treatment of T2DM-related inflammation and vascular injury by regulating cellular crosstalk in the islet microenvironment.Frontiers in endocrinology · 2025Review
- Interactions between islet-resident macrophages and β cells in diabetes.Frontiers in immunology · 2025Review
- Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.Diabetologia · 2025Article
- Review
- Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption.Communications biology · 2024Article
- CircRNA LOC729852 promotes bladder cancer progression by regulating macrophage polarization and recruitment via the miR-769-5p/IL-10 axis.Journal of cellular and molecular medicine · 2024Article
- RUNX1 promotes angiogenesis in colorectal cancer by regulating the crosstalk between tumor cells and tumor associated macrophages.Biomarker research · 2024Article
126 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Determination of signaling pathways that regulate beta-cell replication is critical for beta-cell therapy. Here, we show that blocking pancreatic macrophage infiltration after pancreatic duct ligation (PDL) completely inhibits beta-cell proliferation. The TGFβ superfamily signaling inhibitor SMAD7 was significantly up-regulated in beta cells after PDL. Beta cells failed to proliferate in response to PDL in beta-cell-specific SMAD7 mutant mice. Forced expression of SMAD7 in beta cells by itself was sufficient to promote beta-cell proliferation in vivo. M2, rather than M1 macrophages, seem to be the inducers of SMAD7-mediated beta-cell proliferation. M2 macrophages not only release TGFβ1 to directly induce up-regulation of SMAD7 in beta cells but also release EGF to activate EGF receptor signaling that inhibits TGFβ1-activated SMAD2 nuclear translocation, resulting in TGFβ signaling inhibition. SMAD7 promotes beta-cell proliferation by increasing CyclinD1 and CyclinD2, and by inducing nuclear exclusion of p27. Our study thus reveals a molecular pathway to potentially increase beta-cell mass through enhanced SMAD7 activity induced by extracellular stimuli.
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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.