| 19288266 |
Grande MT, Arevalo M, Nunez A, Cannata-Andia JB, Santos E, Lopez-Novoa JM: Targeted genomic disruption of H-ras and N-ras has no effect on early renal changes after unilateral ureteral ligation. J Refract Surg. 2008 Jun;24(6):626-32.
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, alpha-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, alpha-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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