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A Role for CD133 in Stem Cell-Mediated Kidney Repair

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Review of “Role of CD133 Molecule in Wnt Response and Renal Repair” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Boosting endogenous kidney repair mechanisms may halt the formation of excess fibrous connective tissue in an organ during reparative processes (fibrosis) and the subsequent development of chronic kidney disease [1, 2]. In the human kidney, studies have suggested that cells expressing the stem cell-associated pentaspan-trans-membrane glycoprotein CD133 (or prominin-1) [3] may represent resident renal progenitor cells (RPCs) implicated in kidney repair [4, 5]. Now, a new study from the laboratory of Benedetta Bussolati (University of Torino, Italy) has sought to understand the biological function of CD133-positive RPCs during the various phases of kidney damage [6]. Will this new study lead to new understanding and new advances in kidney repair?

Brossa et al. started their investigations by characterizing adult human RPCs by RNA sequencing, discovering that, other than CD133, RPCs also expressed a number of known kidney stem/progenitor markers. However, when studying RPC dynamics in an in vitro model of kidney cell damage, the authors learned that CD133+ RPCs rapidly lost CD133 expression and then upregulated genes required for the reparative process and modulated their phenotype into a more mesenchymal-like state. Interestingly, as the reparative process finished and the recovery phase began, RPCs regained CD133 expression. Furthermore, knockdown of CD133 in RPCs led to a muted regenerative reaction in response to injury, including a decrease in the clonal expansion of RPCs and an increase in the levels of senescent RPCs, which the authors linked to the deregulation of the Wnt/beta-catenin signaling pathway. 

Overall, this suggested to the authors that, in response to injury, RPCs employ Wnt signaling to shift phenotype and dedifferentiate into a CD133-negative form to effect repair, before returning to a CD133-positive “resting” form following the resolution of the injury.

For more on the function of CD133 and stem/progenitor-mediated endogenous repair mechanisms in the adult, stay tuned to the Stem Cells Portal!

References

  1. Bydash JR and Ishani A, Acute kidney injury and chronic kidney disease: a work in progress. Clin J Am Soc Nephrol 2011;6:2555-7.
  2. Coca SG, Singanamala S, and Parikh CR, Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-8.
  3. Miraglia S, Godfrey W, Yin AH, et al., A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 1997;90:5013-21.
  4. Angelotti ML, Ronconi E, Ballerini L, et al., Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 2012;30:1714-25.
  5. Hansson J, Hultenby K, Cramnert C, et al., Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney. Hum Pathol 2014;45:382-93.
  6. Brossa A, Papadimitriou E, Collino F, et al., Role of CD133 Molecule in Wnt Response and Renal Repair. STEM CELLS Translational Medicine 2018;7:283-294.