尿路上皮细胞介导的Sonic Hedgehog信号通路在肾盂输尿管蠕动功能障碍所致肾积水中的实验研究

批准号:
82000724
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
任川川
依托单位:
学科分类:
尿控及排尿功能异常
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
任川川
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中文摘要
先天性肾积水(CHN)是胎儿和儿童最常见的泌尿系异常,可致肾实质萎缩和间质纤维化,进而导致终末期肾病。但约50%的输尿管扩张患儿并未发现机械梗阻,且肾盂输尿管壁结构无异常。因此,我们假设输尿管蠕动功能障碍在CHN发病机制中起重要作用。目前在肾盂和输尿管发现2种起搏细胞:位于肾盂的非典型平滑肌细胞和肾盂输尿管的Cajal间质样细胞。研究显示sonic Hedgehog信号通路在肾盂输尿管尿路上皮细胞及输尿管平滑肌细胞的分化和发育中起重要作用。但是输尿管蠕动的分子机制和生理功能尚未完全明确。本研究拟体外培养小鼠胚胎肾盂输尿管和肾盂输尿管黏膜剥脱动物模型探索尿路上皮细胞及Hedgehog信号通路在肾盂输尿管蠕动功能和起搏细胞分化发育中的调控及其在肾积水发病机制中的作用,为疾病诊治提供参考。
英文摘要
Congenital hydronephrosis (CHN) is the most common fetal and childhood urinary system abnormalities. Which could eventually result in progressive renal tubular atrophy and interstitial fibrosis, and then end-stage renal disease. It has reported that nearly 50% of the children with ureteral dilatation did not find mechanical obstruction, and the renal pelvis and ureter wall had no structural abnormalities. Therefore, we assume that ureteral peristalsis dysfunction plays an important role in the pathogenesis of CHN. Two types of special pacemaker cells with electrical rhythmicity have been identified in the renal pelvis and ureter. Atypical SMCs are mainly located within the most proximal region of the renal pelvis and the interstitial cells of Cajal (ICC) - like cells are located sparsely throughout the renal pelvis and ureter. It has been found that the sonic hedgehog signaling pathway play an important role in the differentiation and development of urothelium and ureteral smooth muscle cells. However, the molecular mechanism and physiological functions of the ureteral peristaltic machinery are still ill-defined. The present study was to investigate the regulation of urothelium and snoic hedgehog signaling pathway in the peristalsis function of pyeloureter and the differentiation and development of pacemaker cells, as well as its role in the pathogenesis of hydronephrosis, in order to provide a better understanding of CHN and diagnostic and treatmental references.
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DOI:10.3760/cma.j.cn101070-20230615-00487
发表时间:2024
期刊:中华实用儿科临床杂志
影响因子:--
作者:任川川;程光阳;李晓洁;王焱;冶卓;张国贤;王庆伟;文建国
通讯作者:文建国
DOI:--
发表时间:2023
期刊:Journal of Cancer Therapy
影响因子:--
作者:Chamini Kumari Hemathilaka Wijelath Achchillage;Chuanchuan Ren
通讯作者:Chuanchuan Ren
国内基金
海外基金
