PMID- 25408545 OWN - NLM STAT- MEDLINE DCOM- 20150507 LR - 20200411 IS - 1096-9896 (Electronic) IS - 0022-3417 (Print) IS - 0022-3417 (Linking) VI - 235 IP - 5 DP - 2015 Apr TI - BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization. PG - 731-44 LID - 10.1002/path.4484 [doi] AB - 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. CI - Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. FAU - Li, Min AU - Li M AD - Renal Research Laboratory, Fondazione D'Amico per la Ricerca sulle Malattie Renali & Fondazione IRCCS Ca', Granda Ospedale Maggiore Policlinico, Milano, Italy. FAU - Armelloni, Silvia AU - Armelloni S FAU - Zennaro, Cristina AU - Zennaro C FAU - Wei, Changli AU - Wei C FAU - Corbelli, Alessandro AU - Corbelli A FAU - Ikehata, Masami AU - Ikehata M FAU - Berra, Silvia AU - Berra S FAU - Giardino, Laura AU - Giardino L FAU - Mattinzoli, Deborah AU - Mattinzoli D FAU - Watanabe, Shojiro AU - Watanabe S FAU - Agostoni, Carlo AU - Agostoni C FAU - Edefonti, Alberto AU - Edefonti A FAU - Reiser, Jochen AU - Reiser J FAU - Messa, Piergiorgio AU - Messa P FAU - Rastaldi, Maria Pia AU - Rastaldi MP LA - eng GR - R01 DK073495/DK/NIDDK NIH HHS/United States GR - R01 DK089394/DK/NIDDK NIH HHS/United States GR - DK073495/DK/NIDDK NIH HHS/United States GR - DK089394/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150107 PL - England TA - J Pathol JT - The Journal of pathology JID - 0204634 RN - 0 (Actin Depolymerizing Factors) RN - 0 (Actins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN132 microRNA, human) RN - 0 (MIRN132 microRNA, mouse) RN - 0 (MIRN134 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Mirn134 microRNA, mouse) RN - 0 (Recombinant Proteins) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.1 (Lim Kinases) SB - IM MH - 3T3 Cells MH - Actin Cytoskeleton/*drug effects/metabolism/pathology MH - Actin Depolymerizing Factors/metabolism MH - Actins/*metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Disease Models, Animal MH - Gene Expression Regulation MH - Glomerulosclerosis, Focal Segmental/chemically induced/genetics/metabolism/pathology/*prevention & control MH - Larva/drug effects/metabolism MH - Lim Kinases/metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/*metabolism MH - Phosphorylation MH - Podocytes/*drug effects/metabolism/pathology MH - Polymerization MH - Proteinuria/metabolism/prevention & control MH - RNA Interference MH - Receptor, trkB/metabolism MH - Recombinant Proteins/pharmacology MH - Signal Transduction/drug effects MH - Time Factors MH - Transfection MH - Zebrafish PMC - PMC4356648 MID - NIHMS644407 OTO - NOTNLM OT - actin cytoskeleton OT - adriamycin nephropathy OT - brain-derived neurotrophic factor OT - podocyte EDAT- 2014/11/20 06:00 MHDA- 2015/05/08 06:00 PMCR- 2016/04/01 CRDT- 2014/11/20 06:00 PHST- 2014/05/28 00:00 [received] PHST- 2014/10/17 00:00 [revised] PHST- 2014/11/11 00:00 [accepted] PHST- 2014/11/20 06:00 [entrez] PHST- 2014/11/20 06:00 [pubmed] PHST- 2015/05/08 06:00 [medline] PHST- 2016/04/01 00:00 [pmc-release] AID - 10.1002/path.4484 [doi] PST - ppublish SO - J Pathol. 2015 Apr;235(5):731-44. doi: 10.1002/path.4484. Epub 2015 Jan 7.