title: Melatonin protects podocytes from angiotensin II-induced injury in an in vitro diabetic nephropathy model.
abstract: Diabetic nephropathy (DN) is a severe renal disorder characterized by podocyte damage and accumulation of extracellular matrix leading to further glomerulosclerosis, possibly via the activation of inflammatory signaling and the generation of oxidative stress. Melatonin has been considered a robust anti‑oxidant, and is able to attenuate DN in several animal models. In the present study, cell viability was examined by CCK-8 assay. Cell apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential (MMP) levels were measured by flow cytometry. Western blot analysis was performed to detect the expression of Nephrin, B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax), Bcl-2, Caspase-3, Janus kinase (JAK)2 and Signal transducer and activator of transcription (STAT)3 in podocytes. Based on an in vitro podocyte injury model, the present study found that the application of melatonin significantly reduced AngII‑induced apoptosis and increased the proliferative rate of cells, as evidenced by decreased expression levels of apoptotic proteins, including Caspase‑3 and Bax, and a change in the ratio of Bax/Bcl‑2. Further investigation demonstrated that a reduction in oxidative stress and the recovery of mitochondrial function were involved in this protective effect. In addition, the Jak/STAT signaling pathway was inhibited, indicating that cytokine‑mediated inflammation was also targeted by melatonin. The present study demonstrated for the first time, to the best our knowledge, that melatonin exerted an anti-apoptotic effect in AngII-mediated podocyte injury, and indicates a possible mechanism to explain the protective effect of melatonin in DN.
authors.affiliation: Department of Integrated Wards, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Ji
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D053612:Janus Kinases / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050791:STAT Transcription Factors; D051028:bcl-2-Associated X Protein; D000804:Angiotensin II; D053612:Janus Kinases; D053148:Caspase 3; D008550:Melatonin