Kidney-specific knockout of Sav1 in the mouse promotes hyperproliferation of renal tubular epithelium through suppression of the Hippo pathway.
作者： Tomoki Kai , Yoshiyuki Tsukamoto , Naoki Hijiya , Akinori Tokunaga , Chisato Nakada
DOI: 10.1002/PATH.4706
关键词:
摘要: We have previously reported that Salvador homologue 1 (SAV1), a component of the Hippo pathway, is significantly down-regulated in high-grade clear cell renal carcinoma (ccRCC) due to 14q copy number loss, and this down-regulation contributes proliferation survival tubular epithelial cells through activation Yes-associated protein (YAP1), downstream target pathway. However, impact SAV1 loss on kidney vivo remained be determined. To address issue, we generated kidney-specific Sav1-knockout (Cdh16-Cre;Sav1(fl/fl) ) mice. Sav1 deficiency enhanced Cdh16-Cre;Sav1(fl/fl) mice, accompanied by nuclear localization Yap1, suggesting suppression tubules also caused structural cellular abnormalities cells, including significant enlargement their nuclei. Furthermore, mice developed both glomerular cysts. Although lining cysts showed no atypia, those variations size shape, which became more severe as aged. In aged observed focal disruption proximal perivascular lymphocytic infiltration. conclusion, required for maintenance growth, structure under physiological conditions, its leads acquisition signalling.
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