PUBLICATION
BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization
- Authors
- Li, M., Armelloni, S., Zennaro, C., Wei, C., Corbelli, A., Ikehata, M., Berra, S., Giardino, L., Mattinzoli, D., Watanabe, S., Agostoni, C., Edefonti, A., Reiser, J., Messa, P., Rastaldi, M.P.
- ID
- ZDB-PUB-170214-267
- Date
- 2015
- Source
- The Journal of pathology 235: 731-44 (Journal)
- Registered Authors
- Keywords
- actin cytoskeleton, adriamycin nephropathy, brain-derived neurotrophic factor, podocyte
- MeSH Terms
-
- 3T3 Cells
- Actin Cytoskeleton/drug effects*
- Actin Cytoskeleton/metabolism
- Actin Cytoskeleton/pathology
- Actin Depolymerizing Factors/metabolism
- Actins/metabolism*
- Animals
- Brain-Derived Neurotrophic Factor/pharmacology*
- Disease Models, Animal
- Gene Expression Regulation
- Glomerulosclerosis, Focal Segmental/chemically induced
- Glomerulosclerosis, Focal Segmental/genetics
- Glomerulosclerosis, Focal Segmental/metabolism
- Glomerulosclerosis, Focal Segmental/pathology
- Glomerulosclerosis, Focal Segmental/prevention & control*
- Larva/drug effects
- Larva/metabolism
- Lim Kinases/metabolism
- Male
- Mice
- Mice, Inbred BALB C
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Phosphorylation
- Podocytes/drug effects*
- Podocytes/metabolism
- Podocytes/pathology
- Polymerization
- Proteinuria/metabolism
- Proteinuria/prevention & control
- RNA Interference
- Receptor, trkB/metabolism
- Recombinant Proteins/pharmacology
- Signal Transduction/drug effects
- Time Factors
- Transfection
- Zebrafish
- PubMed
- 25408545 Full text @ J. Pathol.
Citation
Li, M., Armelloni, S., Zennaro, C., Wei, C., Corbelli, A., Ikehata, M., Berra, S., Giardino, L., Mattinzoli, D., Watanabe, S., Agostoni, C., Edefonti, A., Reiser, J., Messa, P., Rastaldi, M.P. (2015) BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization. The Journal of pathology. 235:731-44.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping