title: A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications.
abstract: Diabetic nephropathy (DN), a microvascular complication occurring in approximately 20-40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed.
authors.affiliation: Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; Division of Cardiology and Cardiac Rehabilitation, "S. Maugeri" Foundation, IRCCS, Institute of Cassano Murge, 70020 Cassano delle Murge, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conserva
authors.affiliation: Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.affiliation: Molecular Medicine Center, Section of Nephrology, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Papale
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055432:Metabolomics; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D012323:RNA Processing, Post-Transcriptional; D012307:Risk Factors; D049490:Systems Biology / Q000379:methods
chemical_list: D005819:Genetic Markers