ArticleThe Journal of biological chemistry2020
Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- Article
- Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.Molecular psychiatry · 2022Article
- The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?Biomedicines · 2022Review
- The Role of Diet in Regulation of Macrophages Functioning.Biomedicines · 2022Review
- Retinal Src homology region 2-containing protein tyrosine phosphatase 2 silencing alleviates diabetic retinopathy via suppressing inflammatory response and oxidative stress by regulating Yes-associated protein 1 activity.Experimental animals · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- SHP2 allosteric inhibitor TK-453 alleviates psoriasis-like skin inflammation in mice via inhibition of IL-23/Th17 axis.iScience · 2022Article
- Interleukin-18 in metabolism: From mice physiology to human diseases.Frontiers in endocrinology · 2022Review
- Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.Acta pharmaceutica Sinica. B · 2022Article
- Single-Chain Fragment Variables Targeting Leukocidin ED Can Alleviate the Inflammation ofInternational journal of molecular sciences · 2021Article
- Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis.Nature communications · 2021Article
- Anti-Vaccines · 2021Article
- The Role of Protein Tyrosine Phosphatases in Inflammasome Activation.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both
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