ArticleScientific reports2017
Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver fibrosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- SHP-1 agonist SC-43 limits methicillin-resistant Staphylococcus aureus infection through inhibition of heme biosynthesis.EMBO molecular medicine · 2026Article
- Article
- SHP1 overexpression ameliorates renal fibrosis via inhibition of STAT3 signaling and glycolysis reprogramming.Scientific reports · 2025Article
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Loss of neutrophil Shp1 produces hemorrhagic and lethal acute lung injury.bioRxiv : the preprint server for biology · 2024Article
- The positive feedback loop of MAD2L1/TYK2/STAT3 induces progression in B-cell acute lymphoblastic leukaemia.Journal of cancer research and clinical oncology · 2023Article
- Targeting pathogenic macrophages by the application of SHP-1 agonists reduces inflammation and alleviates pulmonary fibrosis.Cell death & disease · 2023Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma.Molecular medicine (Cambridge, Mass.) · 2022Article
- S-Acetyl-Glutathione Attenuates Carbon Tetrachloride-Induced Liver Injury by Modulating Oxidative Imbalance and Inflammation.International journal of molecular sciences · 2022Article
- Evaluation of the Mechanism of Jiedu Huazhuo Quyu Formula in Treating Wilson's Disease-Associated Liver Fibrosis by Network Pharmacology Analysis and Molecular Dynamics Simulation.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Lipophilic Constituents inFrontiers in pharmacology · 2022Article
- The tyrosine phosphatase SHP2 controls TGFβ-induced STAT3 signaling to regulate fibroblast activation and fibrosis.Nature communications · 2018Article
- Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling throughPakistan journal of medical sciencesArticle
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to investigate the role of src-homology protein tyrosine phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3) pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1 activity, was evaluated in two fibrosis mouse models by carbon tetrachloride induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate cells (HSCs) were used for mechanistic investigations. The results showed that SHP-1 protein primarily localized in fibrotic areas of human and mouse livers. SC-43 treatment reduced the activated HSCs and thus effectively prevented and regressed liver fibrosis in both fibrosis mouse models and improved mouse survival. In vitro studies revealed that SC-43 promoted HSC apoptosis, increased the SHP-1 activity and inhibited phospho-STAT3. The enhanced SHP-1 activity in HSCs significantly inhibited HSC proliferation, whereas SHP-1 inhibition rescued SC-43-induced HSC apoptosis. Furthermore, SC-43 interacted with the N-SH2 domain of SHP-1 to enhance the activity of SHP-1 as its antifibrotic mechanism. In conclusion, the SHP-1-STAT3 pathway is crucial in fibrogenesis. SC-43 significantly ameliorates liver fibrosis through SHP-1 upregulation. A SHP-1-targeted antifibrotic therapy may represent a druggable strategy for antifibrotic drug discovery.
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