Targeted genomic disruption of H-ras and N-ras has no effect on early renal changes after unilateral ureteral ligation

• Published in: World journal of urology 2009-12, Vol.27 (6), p.787-797
• Main Authors: Grande, María T., Arévalo, Miguel, Núñez, Alejandro, Cannata-Andía, Jorge B., Santos, Eugenio, López-Novoa, José M.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Caspase 3 - metabolism; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibronectins - metabolism; Fibrosis; Genome; Kidney - metabolism; Kidney - pathology; Kidney Diseases - pathology; Kidney Diseases - physiopathology; Ligation; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrology; Nephrology. Urinary tract diseases; Oncology; Original Article; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Ureter - physiology; Ureteral Obstruction - pathology; Ureteral Obstruction - physiopathology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urology
• ISSN: 0724-4983; 1433-8726
• DOI: 10.1007/s00345-009-0399-8

Purpose To assess the contribution of two different Ras monomeric GTPases isoforms H- and N-Ras in the early changes associated to obstructive nephropathy induced by unilateral ureteral obstruction (UUO). Methods UUO was performed in N-ras ( N-ras −/− ) and H-ras ( H-ras −/− ) knock-out mice and control ( H-ras +/+ /N-ras +/+ ) mice of C57Bl/6 background. Fibronectin, α-smooth muscle actin, cleaved caspase-3, ki-67, Ras-GTP, pERK, and pAkt expression was analyzed by western blot and/or immunohistochemistry. Ras isoforms activation and caspase activity were determined by both western blot and ELISA. Results Three days after UUO, obstructed (O) kidneys of H-ras −/− , N-ras −/− and H-ras +/+ /N-ras +/+ mice showed no significant differences in activated total ras, pERK1/2, pAkt, total Akt levels, fibronectin, α-SMA expression, cell proliferation, and activated caspase-3. The morphological alterations in the O kidneys, revealed by histological and immunohistochemical studies, were also similar in H-ras −/− , N-ras −/− , and H-ras +/+ /N-ras +/+ mice. Conclusions These data suggest that the activation of H-ras and N-ras isoforms does not play a major role in the early renal damage induced by UUO.