Metformin inhibits polyphosphate-induced hyper-permeability and inflammation
| العنوان: | Metformin inhibits polyphosphate-induced hyper-permeability and inflammation |
|---|---|
| المؤلفون: | Saeedeh Mehraban, Milad Hashemzehi, Reyhaneh Behnam-Rassouli, Mohammad-Hassan Arjmand, Farzad Rahmani, Maryam Fakhraie, Seyed Mahdi Hassanian, Mikhail Ryzhikov, Sayyed-Hadi Sayyed-Hosseinian, Farnaz Barneh, Mohieddin Jafari, Najmeh Jaberi, Mohammad Shabani, Seyede leili Adel barkhordar, Majid Khazaei, Gordon A. Ferns, Fatemeh Ariakia, Fereshteh Asgharzadeh, Amir Avan, Atena Soleimani |
| المساهمون: | Research Program in Systems Oncology, Research Programs Unit |
| المصدر: | International immunopharmacology. 99 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Anti-Inflammatory Agents, Vascular permeability, 030204 cardiovascular system & hematology, VASCULAR-PERMEABILITY, COMPLEMENT, ACTIVATION, chemistry.chemical_compound, Mice, 0302 clinical medicine, AMP-Activated Protein Kinase Kinases, Cell Movement, Polyphosphates, Immunology and Allergy, 0303 health sciences, Factor XII, Mice, Inbred BALB C, MOLECULAR-MECHANISMS, Chemistry, TOR Serine-Threonine Kinases, PLATELETS, Metformin, 3. Good health, FACTOR-KAPPA-B, 317 Pharmacy, medicine.symptom, Oxidation-Reduction, medicine.drug, Signal Transduction, Immunology, COAGULATION, Bradykinin, Inflammation, Capillary Permeability, 03 medical and health sciences, Sepsis, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, Platelet activation, PI3K/AKT/mTOR pathway, 030304 developmental biology, Pharmacology, AMPK, digestive system diseases, INORGANIC POLYPHOSPHATE, Disease Models, Animal, Oxidative Stress, MAMMALIAN TARGET, Cancer research, AMPK signaling, RESPONSES |
| الوصف: | Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic shortand systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/ anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases. |
| وصف الملف: | application/pdf |
| تدمد: | 1878-1705 1567-5769 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98d18bd58bde364224f82e05f990c732Test https://pubmed.ncbi.nlm.nih.gov/34271418Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....98d18bd58bde364224f82e05f990c732 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18781705 15675769 |
|---|