ArticleMolecular and cellular biology2013
Epithelial tyrosine phosphatase SHP-2 protects against intestinal inflammation in mice.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Microplastic exposure is associated with enhanced PI3K-Akt signaling in DSS-induced colitis: integrated bioinformatics analyses andFrontiers in pharmacology · 2026Article
- Review
- Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis.Acta pharmaceutica Sinica. B · 2024Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy.Frontiers in oncology · 2022Review
- Roles of Src family kinase, Ras, and mTOR signaling in intestinal epithelial homeostasis and tumorigenesis.Cancer science · 2021Review
- SHP2 regulates the development of intestinal epithelium by modifying OSTERIXFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands.Frontiers in immunology · 2021Review
- Alternative splicing reverses the cell-intrinsic and cell-extrinsic pro-oncogenic potentials of YAP1.The Journal of biological chemistry · 2020Article
- Leukocyte immunoglobulin-like receptor B4 protects against cardiac hypertrophy via SHP-2-dependent inhibition of the NF-κB pathway.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Transforming growth factor beta 1 impairs benign prostatic luminal epithelial cell monolayer barrier function.American journal of clinical and experimental urology · 2020Article
- Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in Sepsis.EBioMedicine · 2019Article
- Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8Frontiers in immunology · 2019Article
- The tyrosine phosphatase Shp-2 confers resistance to colonic inflammation by driving goblet cell function and crypt regeneration.The Journal of pathology · 2019Article
- Protein Tyrosine Phosphatases: Regulators of CD4 T Cells in Inflammatory Bowel Disease.Frontiers in immunology · 2018Review
- SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.Scientific reports · 2017Article
- Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria.Scientific reports · 2017Article
- Gata4 is critical to maintain gut barrier function and mucosal integrity following epithelial injury.Scientific reports · 2016Article
- SHP-2 Phosphatase Prevents Colonic Inflammation by Controlling Secretory Cell Differentiation and Maintaining Host-Microbiota Homeostasis.Journal of cellular physiology · 2016Article
- SHP-2 phosphatase contributes to KRAS-driven intestinal oncogenesis but prevents colitis-associated cancer development.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polymorphisms of PTPN11 encoding SHP-2 are biomarkers for ulcerative colitis (UC) susceptibility. However, their functional relevance is unknown. We thus investigated the role of epithelial SHP-2 in the control of intestinal homeostasis. Mice with an intestinal epithelial cell-specific SHP-2 deletion (SHP-2(IEC-KO) mice) were generated. Control and SHP-2(IEC-KO) mice were monitored for clinical symptoms and sacrificed for histological staining and Western blot analyses. Cytokines and chemokines, as well as intestinal permeability, were quantified. SHP-2 mRNA expression was evaluated in control and UC patients. SHP-2(IEC-KO) mice showed growth retardation compared to control littermates and rapidly developed severe colitis. Colon architecture was markedly altered with infiltration of immune cells, crypt abscesses, neutrophil accumulation, and reduced goblet cell numbers. Decreased expression of claudins was associated with enhanced intestinal permeability in mutant SHP-2(IEC-KO) mice. Inflammatory transcription factors Stat3 and NF-κB were hyperactivated early in the mutant colonic epithelium. Levels of several epithelial chemokines and cytokines were markedly enhanced in SHP-2(IEC-KO) mice. Of note, antibiotic treatment remarkably impaired the development of colitis in SHP-2(IEC-KO) mice. Finally, SHP-2 mRNA levels were significantly reduced in intestinal biopsy specimens from UC patients. Our results establish intestinal epithelial SHP-2 as a critical determinant for prevention of gut inflammation.
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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.