ArticleScience translational medicine2022
CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis.
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Who cites it
63 citing papers in PubMed, 73 citations in OpenAlex.
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- Research advances on CD47 in digestive system cancers: from molecular mechanisms to clinical translation.Molecular medicine (Cambridge, Mass.) · 2026Review
- Article
- Drug Development for MASH-Related Compensated Cirrhosis: Past, Present and Future.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Hepatocyte CD146 and soluble CD146 promote hepatic stellate cell activation via the integrin αvβ1-p38 MAPK signaling axis to drive liver fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- mRNA-laden LNP-enabled in situ CAR-macrophage alleviates liver fibrosis via inhibiting activated HSCs and modulating the immune microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hepatocyte BDNF Acts as a Novel Immune Checkpoint to Restrain TLR4-Mediated Acute Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypothermic machine perfusion protects DCD graft liver from ischemia‑reperfusion injury by enhancing macrophage efferocytosis via KLF2‑NLRP3 signaling.International journal of molecular medicine · 2026Article
- Metabolic Dysfunction-associated Steatotic Liver Disease and Chronic Kidney Disease: From Epidemiology and Pathophysiology to Clinical Prediction and Treatment Options.Journal of clinical and translational hepatology · 2026Review
- MLKL in liver parenchymal cells promotes liver cancer in murine metabolic dysfunction-associated steatotic liver disease.Cell death & disease · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Targeting efferocytosis for tissue regeneration: From microenvironment reprogramming to clinical translation.Theranostics · 2026Review
- Cleaning, Chasing and Calming: Promising Paradigms of Senotherapy in Aging-Related Diseases.International journal of biological sciences · 2026Review
- The CD47 signaling axis regulates the formation and vulnerability of atherosclerotic plaques: mechanism analysis and targeting strategies.Frontiers in immunology · 2026Review
- Immune activation induced by dysregulated lipid metabolism in the pathogenesis of type 2 diabetes.World journal of diabetes · 2025Review
- Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Cancer gene therapy: historical perspectives, current applications, and future directions.Functional & integrative genomics · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Necroptosis contributes to hepatocyte death in nonalcoholic steatohepatitis (NASH), but the fate and roles of necroptotic hepatocytes (necHCs) in NASH remain unknown. We show here that the accumulation of necHCs in human and mouse NASH liver is associated with an up-regulation of the "don't-eat-me" ligand CD47 on necHCs, but not on apoptotic hepatocytes, and an increase in the CD47 receptor SIRPα on liver macrophages, consistent with impaired macrophage-mediated clearance of necHCs. In vitro, necHC clearance by primary liver macrophages was enhanced by treatment with either anti-CD47 or anti-SIRPα. In a proof-of-concept mouse model of inducible hepatocyte necroptosis, anti-CD47 antibody treatment increased necHC uptake by liver macrophages and inhibited markers of hepatic stellate cell (HSC) activation, which is responsible for liver fibrogenesis. Treatment of two mouse models of diet-induced NASH with anti-CD47, anti-SIRPα, or AAV8-H1-shCD47 to silence CD47 in hepatocytes increased the uptake of necHC by liver macrophages and decreased markers of HSC activation and liver fibrosis. Anti-SIRPα treatment avoided the adverse effect of anemia found in anti-CD47-treated mice. These findings provide evidence that impaired clearance of necHCs by liver macrophages due to CD47-SIRPα up-regulation contributes to fibrotic NASH, and suggest therapeutic blockade of the CD47-SIRPα axis as a strategy to decrease the accumulation of necHCs in NASH liver and dampen the progression of hepatic fibrosis.
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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.