Resilient CD133+CD24+ Kidney Progenitor Cells Drive Hypoxic Injury Recovery via HIF1A, EGFR, and EDN1 Expression

Kidney progenitor cells play a crucial role in the repair and regeneration of renal tubules following injury. This study investigates the differential responses of human renal tubular precursor TERT (HRTPT) CD133+CD24+ kidney progenitor cells and Human renal epithelial cell 24 TERT (HREC24T) CD133-CD24+ non-progenitor cells to hypoxic conditions, as well as their gene expression profiles. Whole transcriptome sequencing revealed distinct molecular characteristics, with HRTPT cells exhibiting enrichment in pathways associated with human and mouse embryonic stem cell pluripotency and hypoxia response. In vitro experiments demonstrated that HRTPT cells are more resistant to hypoxia, showing minimal cell death and a 100-fold increase in HIF1A protein levels. In contrast, HREC24T cells exhibited significant cell death and only a modest increase in HIF1A protein. Functional network analysis identified a central role for Endothelin-1 (EDN1) in the interaction between HIF1A and epidermal growth factor (EGF) signaling pathways. These results suggest that CD133+CD24+ kidney progenitor cells have enhanced survival mechanisms under hypoxic stress, enabling them to effectively proliferate and replace damaged tubular cells. This study provides novel insights into the protective role of kidney progenitor cells in renal injury and their potential therapeutic applications in kidney regeneration