Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus).
Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.
Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis.Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis.
Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis.