BDNF repairs podocyte damage by microRNA-mediated increase of actin polymerization

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)731-744
Number of pages14
JournalJournal of Pathology
Volume235
Issue number5
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • actin cytoskeleton
  • adriamycin nephropathy
  • brain-derived neurotrophic factor
  • podocyte

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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