Abstract
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.
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Acknowledgments
The authors wish to thank Ms. Angustias Pérez for his invaluable skilful technical assistance in histology procedures. This study was supported by grants from Spanish Ministerio de Ciencia y Tecnología (BFU2004-00285/BFI and SAF 2003-04177), Instituto de Salud Carlos III (RD06/0016/013: RedinRen) and Junta de Castilla y León (SA 001/C05).
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The authors declare that they have no conflict of interest.
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Grande, M.T., Arévalo, M., Núñez, A. et al. Targeted genomic disruption of H-ras and N-ras has no effect on early renal changes after unilateral ureteral ligation. World J Urol 27, 787–797 (2009). https://doi.org/10.1007/s00345-009-0399-8
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DOI: https://doi.org/10.1007/s00345-009-0399-8