Abstract
Congenital hydronephrosis caused by ureteropelvic junction obstruction (UPJO) eventually leads to renal interstitial fibrosis and atrophy, after a series of pathophysiological problems. Renal repair after injury depends on renal stem cells. This study aimed to determine the expression of renal stem cell marker CD133 in children of different ages and the regulatory effect of stem cell microenvironment. Renal stem cells from children of different ages were identified and screened out by flow cytometry in the study. Children with hydronephrosis were divided into neonates, infants, preschool age, school age, and adolescents groups. A hypoxic cell model prepared with CoCl2 was developed to detect the effect of hypoxia on the proliferation and apoptosis of renal stem cells. The effect and molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) on the proliferation and apoptosis of renal stem cells were also explored. Both hypoxia and HIF-1α significantly promoted the proliferation of renal stem cells and inhibited cell apoptosis. HIF-1α could bind to the promoter region of proliferating cell nuclear antigen (PCNA) and PROM1 (CD133) to mediate their transcription and expression. The content of CD133+ renal stem cells was the highest in the neonatal group and it decreased with the increase of age. Taken together, this study clarified the effect of age on the content of human renal stem cells and determined the regulatory mechanism of hypoxia on renal stem cells. We expect our results to provide a research basis for the treatment and clinical application of renal stem cells.
Highlights
Congenital hydronephrosis is frequently encountered in pediatric urology resulting from ureteropelvic junction obstruction (UPJO)
The dual-luciferase reporter assay indicated the role of hypoxia-inducible factor (HIF)-1α binding to the proliferating cell nuclear antigen (PCNA) and PROM1 promoters in facilitating gene transcription (Figure 4B and C). These results suggested that HIF-1α bound to the promoter region of PCNA and enhanced its transcription and expression, 317
We collected the samples from children with congenital hydronephrosis at different ages, and our results suggest that CD133 expression is closely associated with the age of patients
Summary
Congenital hydronephrosis is frequently encountered in pediatric urology resulting from ureteropelvic junction obstruction (UPJO). This disease results in many pathological and physiological problems, including renal interstitial edema, focal inflammatory cell infiltration, and degeneration and necrosis of renal tubular epithelial cells, thereby leading to fibrosis and atrophy of renal interstitium eventually [1,2]. The cells are introduced as a therapeutic option for kidney diseases due to the ability of multipotent differentiation, and reparative properties. They induce renewal of renal tissues, regenerating damaged cells, Department of Pediatric General Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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