BDNF repairs podocyte damage by microRNA‐mediated increase of actin polymerization |
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| Authors: | Min Li Silvia Armelloni Cristina Zennaro Changli Wei Alessandro Corbelli Masami Ikehata Silvia Berra Laura Giardino Deborah Mattinzoli Shojiro Watanabe Carlo Agostoni Alberto Edefonti Jochen Reiser Piergiorgio Messa Maria Pia Rastaldi |
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| Affiliation: | 1. Renal Research Laboratory, Fondazione D'Amico per la Ricerca sulle Malattie Renali & Fondazione IRCCS Ca', Granda Ospedale Maggiore Policlinico, Milano, Italy;2. Laboratory of Renal Physiopathology, Department of Medical, Surgical, and Health Sciences, Trieste University, Trieste, Italy;3. Department of Medicine, Rush University Medical Center, Chicago, IL, USA;4. Bio‐imaging Unit, Department of Cardiovascular Clinical Pharmacology, Mario Negri Institute of Pharmacological Research, Milano, Italy;5. ‘L Sacco’ Department of Biomedical and Clinical Sciences, University of Milano, Italy;6. Pediatric Clinic 2, Department of Clinical Sciences and Community Health, Clinica Pediatrica de Marchi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;7. Division of Pediatric Nephrology and Dialysis, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy;8. Division of Nephrology, Dialysis, and Renal Transplant, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy |
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| Abstract: | Idiopathic focal segmental glomerulosclerosis (FSGS) is a progressive and proteinuric kidney disease that starts with podocyte injury. Podocytes cover the external side of the glomerular capillary by a complex web of primary and secondary ramifications. Similar to dendritic spines of neuronal cells, podocyte processes rely on a dynamic actin‐based cytoskeletal architecture to maintain shape and function. Brain‐derived neurotrophic factor (BDNF) is a pleiotropic neurotrophin that binds to the tropomyosin‐related kinase B receptor (TrkB) and has crucial roles in neuron maturation, survival, and activity. In neuronal cultures, exogenously added BDNF increases the number and size of dendritic spines. In animal models, BDNF administration is beneficial in both central and peripheral nervous system disorders. Here we show that BDNF has a TrkB‐dependent trophic activity on podocyte cell processes; by affecting microRNA‐134 and microRNA‐132 signalling, BDNF up‐regulates Limk1 translation and phosphorylation, and increases cofilin phosphorylation, which results in actin polymerization. Importantly, BDNF effectively repairs podocyte damage in vitro, and contrasts proteinuria and glomerular lesions in in vivo models of FSGS, opening a potential new perspective to the treatment of podocyte disorders. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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| Keywords: | podocyte brain‐derived neurotrophic factor adriamycin nephropathy actin cytoskeleton |
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