Abstract: TH-PO319

Role of CD133 Molecule in WNT Response and Renal Repair

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Bussolati, Benedetta, University of Torino , Torino, Italy
  • Papadimitriou, Elli, University of Torino , Torino, Italy
  • Brossa, Alessia, University of Torino , Torino, Italy
Background

The renal CD133+ cells have been indicated as a resident scattered population able to survive and proliferate after injury. However, the biological function of CD133 molecule along with its possible modulation during damage are currently unknown. In the present study, we evaluated the role of stem cell marker CD133 in renal cellular repair at both molecular and functional level.

Methods

CD133 was silenced by two different shRNA against CD133. RNA sequencing was performed on CD133+ and CD133Kd cells after cisplatin damage. Functional Enrichment analysis tool and PANTHER software were used for pathways enrichment analysis. Wnt pathway activation was studied by Western Blot analysis of beta-catenin expression and Luciferase reporter assay for the TCF/LEF promoter. Proliferation, sphere formation, telomere length and senescence were evaluated in CD133+ and CD133Kd cells.

Results

We found that CD133+ cells dedifferentiated after damage, loosing the CD133 signature and acquiring metanephric mesenchymal genes such as SNAIL1 and KLF4 and regenerative genes such as SOX9 and WNT3. CD133 was reacquired in the recovery phase. Lack of CD133 limited cell proliferation after injury and was correlated with deregulation of Wnt signaling pathway. In parallel, CD133-Kd cells showed lower β-catenin levels and TCF/LEF promoter activation in respect to CD133+ cells. Finally, the lack of CD133 impaired clonal generation of spheres while favored senescence.

Conclusion

These data indicate that CD133 may act as a permissive factor for Wnt/beta-catenin signaling, regulating the cell proliferative response after damage, and may limit cell senescence. In addition, CD133 are not stable during damage, but rather undergo a mesenchymal dedifferentiation showing a plastic phenotype.

Funding

  • Government Support - Non-U.S.