Augmenter of liver regeneration (ALR) enhances the proliferation of hepatocytes and accelerates recovery from
acute liver failure in animal models. ALR is expressed in both the liver and kidney; however, the specific location of ALR expression and its
biological effects in the kidney remain unknown. We aimed to investigate the efficacy of ALR in rats with
gentamicin (GM)-induced
acute renal failure (ARF). Rats were randomized into the normal group, GM+saline group, GM+vehicle group, and GM+rrALR group. Blood
urea nitrogen, serum
creatinine, and urine beta-N-acetyl-D-
glucosaminidase were measured, and histological analyses of the kidneys were performed. The expression of ALR
protein was determined by immunohistochemistry and Western blotting. In vitro incorporation of tritiated
thymidine was used to measure the proliferation of renal tubular epithelial cells. In normal rats, the expression of ALR
protein was faint in the medulla and absent in the cortex. However, in ARF rats, ALR expression increased significantly in both the renal cortex and medulla. Histological analyses revealed that treatment with recombinant rat ALR (rrALR) reduced the extent of injury of tubular cells in the renal cortex. Serum/urine biochemical parameters also showed that renal dysfunction was improved by the administration of rrALR.
Intraperitoneal injection of rrALR enhanced the proliferation of tubular cells in vivo. We also confirmed that rrALR could promote the proliferation of renal tubular cells in vitro. These results indicate that rrALR effectively accelerates kidney recovery after ARF induced by
gentamicin, and that the protective effect is associated with enhanced proliferation of renal tubular cells.