Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.
This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.
"Victor Babes" National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, Romania.
Gina
G
Manda
"Victor Babes" National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy Bucharest, 37 Dionisie Lupu, 020022 Bucharest, Romania.
Alexandru-Ionel
AI
Checherita
"Victor Babes" National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy Bucharest, 37 Dionisie Lupu, 020022 Bucharest, Romania.
Maria Victoria
MV
Comanescu
"Victor Babes" National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy Bucharest, 37 Dionisie Lupu, 020022 Bucharest, Romania.
Mihail Eugen
ME
Hinescu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D003928:Diabetic Nephropathies / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D006984:Hypertrophy / Q000473:pathology*; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050199:Podocytes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species