ArticleFrontiers in physiology2017
MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients.
Article in Frontiers in physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Insights Into Gut Barrier Dysfunction and Metabolic Alterations in Mycophenolate-Induced Enteropathy.Basic & clinical pharmacology & toxicology · 2026Article
- Immunosuppressants rewire the gut microbiome-alloimmune axis through time-dependent and tissue-specific mechanisms.Cell communication and signaling : CCS · 2025Article
- Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Immunosuppressant imprecision: multidirectional effects on metabolism and microbiome.Clinical microbiology reviews · 2025Review
- Biopharmaceutical Factors Involved in the Disposition of Mycophenolic Acid: A Comprehensive Review of ADME Properties and Their Potential Impact on Mycophenolic Acid Plasma Exposure.Current drug metabolism · 2025Review
- Formate Metabolism in Shigella flexneri and Its Effect on HeLa Cells at Different Stages during the Infectious Process.Microbiology spectrum · 2023Article
- Mechanisms and modeling of wound repair in the intestinal epithelium.Tissue barriers · 2023Review
- Small Molecule BRD4 Inhibitors Apabetalone and JQ1 Rescues Endothelial Cells Dysfunction, Protects Monolayer Integrity and Reduces Midkine Expression.Molecules (Basel, Switzerland) · 2022Article
- Article
- Current Analytical Strategies in Studying Chromatin-Associated-Proteome (Chromatome).Molecules (Basel, Switzerland) · 2021Review
- Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 -106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients.Pharmacogenomics and personalized medicine · 2021Article
- Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation.Biomolecules · 2020Review
- Reduced Mrp2 surface availability as PI3Kγ-mediated hepatocytic dysfunction reflecting a hallmark of cholestasis in sepsis.Scientific reports · 2020Article
- Midkine activation of CD8Nature communications · 2020Article
- Biomaterial-tight junction interaction and potential impacts.Journal of materials chemistry. B · 2019Review
- Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells.International journal of molecular sciences · 2019Article
- Vancomycin relieves mycophenolate mofetil-induced gastrointestinal toxicity by eliminating gut bacterial β-glucuronidase activity.Science advances · 2019Article
- Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions.PloS one · 2019Article
- The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the present study, we investigated the possible involvement of Midkine dependent PI3K pathway in alteration of TJs under MPA treatment. Caco-2 cells were grown as monolayer to develop TJs and were treated for 72 h with DMSO (control) or MPA in presence and absence of Midkine inhibitor (iMDK) or PI3K inhibitors (LY/AMG). Caco-2 monolayer integrity was assessed by transepithelial electrical resistance (TEER) and FITC-dextran assays. Our functional assays showed that PI3K inhibitors (LY/AMG) can significantly inhibit the compromised TJs integrity of MPA-treated Caco-2 cells monolayer. Chromatin immunoprecipitation analyses showed a significant epigenetic activation of M
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