Studies have reported the presence of renal proximal tubule specific progenitor cells which co-express PROM1 and CD24 markers on the cell surface. The RPTEC/TERT cell line is a telomerase-immortalized proximal tubule cell line that expresses two populations of cells, one co-expressing PROM1 and CD24 and another expressing only CD24, identical to primary cultures of human proximal tubule cells (HPT). The RPTEC/TERT cell line was used by the authors to generate two new cell lines, HRTPT co-expressing PROM1 and CD24 and HREC24T expressing only CD24. The HRTPT cell line has been shown to express properties expected of renal progenitor cells while HREC24T expresses none of these properties. The HPT cells were used in a previous study to determine the effects of elevated glucose concentrations on global gene expression. This study showed the alteration of expression of lysosomal and mTOR associated genes. In the present study, this gene set was used to determine if pure populations of cells expressing both PROM1 and CD24 had different patterns of expression than those expressing only CD24 when exposed to elevated glucose concentrations. In addition, experiments were performed to determine whether cross-talk might occur between the two cell lines based on their expression of PROM1 and CD24. It was shown that the expression of the mTOR and lysosomal genes was altered in expression between the HRTPT and HREC24T cell lines based on their PROM1 and CD24 expression. Using metallothionein (MT) expression as a marker demonstrated that both cell lines produced condition media that could alter the expression of the MT genes. It was also determined that PROM1 and CD24 co-expression was limited in renal cell carcinoma (RCC) cell lines.

Cisplatin (CisPt) is a widely used chemotherapeutic agent. However, its nephrotoxic effects pose significant risks, particularly for the development of acute kidney injury (AKI) and potential progression to chronic kidney disease (CKD). The present study investigates the impact of non-lethal exposure of CisPt to immortalized human renal epithelial precursor TERT cells (HRTPT cells) that co-express PROM1 and CD24, markers characteristic of renal progenitor cells. Over eight serial passages, HRTPT cells were exposed to 1.5 µM CisPt, leading to an initial growth arrest, followed by a gradual recovery of proliferative capacity. Despite maintaining intracellular platinum (Pt) levels, the cells exhibited normal morphology by passage eight (P8), with elevated expression of renal stress and damage markers. However, the ability to form domes was not restored. RNA-seq analysis revealed 516 differentially expressed genes between CisPt-exposed and control cells, with significant correlations to cell cycle and adaptive processes, as determined by the Reactome, DAVID, and Panther analysis programs. The progenitor cells treated with CisPt displayed no identity, or close identity, with cells of the normal human nephron. Additionally, several upregulated genes in P8 cells were linked to cancer cell lines, suggesting a complex interaction between CisPt exposure and cellular repair mechanisms. In conclusion, our study demonstrates that renal progenitor cells can recover from CisPt exposure and regain proliferative potential in the continued presence of both extracellular CisPt and intracellular Pt.