Mechanisms of the proteinuria induced by Rho GTPases.

Abstract:

:Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively active (V14 Rho) or dominant-negative Rho A (N19 Rho) in podocytes. Specific induction of either Rho A construct in podocytes caused albuminuria and foot process effacement along with disruption of the actin cytoskeleton as evidenced by decreased expression of the actin-associated protein synaptopodin. The mechanisms of these adverse effects, however, appeared to be different. Active V14 Rho enhanced actin polymerization, caused a reduction in nephrin mRNA and protein levels, promoted podocyte apoptosis, and decreased endogenous Rho A levels. In contrast, the dominant-negative N19 Rho caused a loss of podocyte stress fibers, did not alter the expression of either nephrin or Rho A, and did not cause podocyte apoptosis. Thus, our findings suggest that Rho A plays an important role in maintaining the integrity of the glomerular filtration barrier under basal conditions, but enhancement of Rho A activity above basal levels promotes podocyte injury.

journal_name

Kidney Int

journal_title

Kidney international

authors

Wang L,Ellis MJ,Gomez JA,Eisner W,Fennell W,Howell DN,Ruiz P,Fields TA,Spurney RF

doi

10.1038/ki.2011.472

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

1075-85

issue

11

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)55214-9

journal_volume

81

pub_type

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