Role of CD133 Molecule in Wnt Response and Renal Repair

Renal repair after injury is dependent on clonal expansion of proliferation-competent cells. In the human kidney, the expression of CD133 characterizes a population of resident scattered cells with resistance to damage and ability to proliferate. However, the biological function of the CD133 molecule is unknown. By RNA sequencing, we found that cells undergoing cisplatin damage lost the CD133 signature and acquired metanephric mesenchymal and regenerative genes such as SNAIL1, KLF4, SOX9, and WNT3. CD133 was reacquired in the recovery phase. In CD133-Kd cells, lack of CD133 limited cell proliferation after injury and was specifically correlated with deregulation of Wnt signaling and E-cadherin pathway. By immunoprecipitation, CD133 appeared to form a complex with E-cadherin and beta-catenin. In parallel, CD133-Kd cells showed lower beta-catenin levels in basal condition and after Wnt pathway activation and reduced TCF/LEF promoter activation in respect to CD133(+) cells. Finally, the lack of CD133 impaired generation of nephrospheres while favoring senescence. These data indicate that CD133 may act as a permissive factor for beta-catenin signaling, preventing its degradation in the cytoplasm. Therefore, CD133 itself appears to play a functional role in renal tubular repair through maintenance of proliferative response and control of senescence.