All-trans retinoic acid ameliorates inflammatory response mediated by TLR4/NF-κB during initiation of diabetic nephropathy |
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| Institution: | 1. Department of Physiology, Biophysics, and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México, DF 07360, Mexico;2. Glomerular Disease Therapeutic Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, United States;3. Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City, D.F., Mexico;1. Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE;2. Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA;1. Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Spain;2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain;3. Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain;4. Nutrition and Genomics Laboratory, J.M.-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA;5. IMDEA Alimentación, Madrid, Spain;6. CNIC, Madrid, Spain;1. HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Nigeria;2. Cardiovascular Unit, Department of Physiology, College of Health sciences, Osun State University, Osogbo, Nigeria;3. Department of Public Health, Kwara State University, Malete, Nigeria;4. Cardiovascular Research Institute and Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea;1. Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada, R3T 2N2;2. Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, R2H 2A6;3. Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, R2H 2A6. |
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| Abstract: | Diabetic nephropathy (DN) is the leading cause of renal failure worldwide and its complications have become a public health problem. Inflammation, oxidative stress and fibrosis play central roles in the progression of DN that lead to renal failure. Potential deleterious effect of inflammation in early evolution of DN is not fully disclosed. Therefore, it is relevant to explore therapies that might modulate this process in order to reduce DN progression. We explored the beneficial effect of all-trans retinoic acid (ATRA) in early inflammation in glomeruli, proximal and distal tubules in streptozotocin (STZ)-induced diabetes. ATRA was administered (1 mg/kg daily by gavage) on days 3 to 21 after STZ administration. It was found that 21 days after STZ injection, diabetic rats exhibited proteinuria, increased natriuresis and loss of body weight. Besides, diabetes induced an increase in interleukins IL-1β, IL-1α, IL-16, IL-13, IL-2; tumor necrosis factor alpha (TNF-α)] and transforming growth factor-beta 1 (TGF-β1), chemokines (CCL2, CCL20, CXCL5 and CXCL7), adhesion molecules (ICAM-1 and L-selectin) and growth factors (GM-CSF, VEGF, PDGF) in glomeruli and proximal tubules, whereas ATRA treatment remarkably ameliorated these alterations. To further explore the mechanisms through which ATRA decreased inflammatory response, the NF-κB/p65 signaling mediated by TLR4 was studied. We found that ATRA administration attenuates the TLR4/NF-κB inflammatory signaling and prevents NF-κB nuclear translocation in glomeruli and proximal tubules. |
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