Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1.

Abstract:

:Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibits the expression of the Wilms' tumor protein (WT1), a transcription factor and master regulator of podocyte differentiation and homeostasis. Decreased expression levels of WT1 lead to downregulation of its target genes PODXL (podocalyxin) and NPHS1 (nephrin), as well as several other genes crucial for the architecture of podocytes, initiating a catastrophic collapse of the entire podocyte-stabilizing system. We found upregulation of miR-193a in isolated glomeruli from individuals with FSGS compared to normal kidneys or individuals with other glomerular diseases. Thus, upregulation of miR-193a provides a new pathogenic mechanism for FSGS and is a potential therapeutic target.

journal_name

Nat Med

journal_title

Nature medicine

authors

Gebeshuber CA,Kornauth C,Dong L,Sierig R,Seibler J,Reiss M,Tauber S,Bilban M,Wang S,Kain R,Böhmig GA,Moeller MJ,Gröne HJ,Englert C,Martinez J,Kerjaschki D

doi

10.1038/nm.3142

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

481-7

issue

4

eissn

1078-8956

issn

1546-170X

pii

nm.3142

journal_volume

19

pub_type

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