Department of Pediatric General Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Bosn J Basic Med Sci. 2021 Jun 1;21(3):313-322. doi: 10.17305/bjbms.2020.4887.
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.
先天性肾盂积水（UPJO）导致的输尿管肾盂连接部梗阻（UPJO）最终会导致肾间质纤维化和萎缩，这是一系列病理生理问题的结果。损伤后的肾脏修复依赖于肾干细胞。本研究旨在确定不同年龄段儿童肾干 细胞标志物 CD133 的表达情况，以及干细胞微环境的调控作用。本研究通过流式细胞术对不同年龄段儿童的肾干细胞进行了鉴定和筛选。将患有肾积水的儿童分为新生儿、婴儿、学龄前、学龄和青少年组。通过 CoCl2 制备缺氧细胞模型，检测缺氧对肾干细胞增殖和凋亡的影响。还探讨了缺氧诱导因子 1-α（HIF-1α）对肾干细胞增殖和凋亡的影响及其分子机制。缺氧和 HIF-1α 均显著促进肾干细胞的增殖，抑制细胞凋亡。HIF-1α 可以与增殖细胞核抗原（PCNA）和 PROM1（CD133）的启动子区域结合，介导它们的转录和表达。CD133+肾干细胞在新生儿组中的含量最高，随年龄增长而减少。综上所述，本研究阐明了年龄对人肾干细胞含量的影响，并确定了缺氧对肾干细胞的调控机制。我们期望我们的研究结果为肾干细胞的治疗和临床应用提供研究基础。
