Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis

Sci Rep. 2018 Mar 22;8(1):5061. doi: 10.1038/s41598-018-23278-6.


Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman's capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / genetics
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Mice
  • Mice, Knockout
  • Nephrosis / chemically induced
  • Nephrosis / genetics*
  • Nephrosis / pathology
  • Neuropeptides / genetics*
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • rac1 GTP-Binding Protein / genetics*


  • Neuropeptides
  • Rac1 protein, mouse
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • rac1 GTP-Binding Protein