title: BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization.
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.
authors.affiliation: Renal Research Laboratory, Fondazione D'Amico per la Ricerca sulle Malattie Renali & Fondazione IRCCS Ca', Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Silvia
authors.initials: S
authors.lastname: Armelloni
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corbelli
authors.forename: Masami
authors.initials: M
authors.lastname: Ikehata
authors.forename: Silvia
authors.initials: S
authors.lastname: Berra
authors.forename: Laura
authors.initials: L
authors.lastname: Giardino
authors.forename: Deborah
authors.initials: D
authors.lastname: Mattinzoli
authors.forename: Shojiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rastaldi
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D054461:Lim Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058105:Polymerization; D011507:Proteinuria / Q000378:metabolism / Q000517:prevention & control; D034622:RNA Interference; D020813:Receptor, trkB / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D015027:Zebrafish
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; C547077:MIRN132 microRNA, human; C546976:MIRN132 microRNA, mouse; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; C551912:Mirn134 microRNA, mouse; D011994:Recombinant Proteins; C579455:BDNF protein, human; D020813:Receptor, trkB; D054461:Lim Kinases
keywords: actin cytoskeleton; adriamycin nephropathy; brain-derived neurotrophic factor; podocyte