The critical role of the proto-oncogene c-Kit in TSC renal cystogenesis.

ABSTRACT: The epithelium of kidney cysts in mouse Tuberous Sclerosis complex (TSC) models and TSC patients is composed of proliferating A-intercalated cells. The ablation of the Foxi1 gene abolished renal cystogenesis in principal cell-specific Tsc1 knockout (Tsc1-KO) mice. RNAseq studies comparing kidneys of Tsc1-KO vs. wild-type (WT) and Tsc1/Foxi1-double-knockout identified c-Kit, a tyrosine kinase receptor (RTK), as a transcript whose expression significantly increased in Tsc1-KO mice. Overexpression of FOXI1 in kidney M-1 cells significantly increased c-Kit expression levels. Kidney cystogenesis was abolished in Tsc1-KO mice by inactivating the c-Kit gene via the generation of Tsc1/c-Kit-double-knockout mice. The treatment of Tsc1-KO mice with Imatinib, a specific inhibitor of c-KIT, significan

SUBMITTER: Zahedi K 

PROVIDER: S-EPMC12905254 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature