微小RNA-17-5p在小儿肾病综合征发病中的作用及其机制研究

doi:10.7499/j.issn.1008-8830.2003329

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摘要

目的分析微小RNA-17-5p（miR-17-5p）在小儿肾病综合征（NS）发病中的意义及其通过激活素A（ActA）/Smads通路对肾足细胞凋亡的影响。方法选取2018年3月至2019年3月收治的55例NS患儿为NS组，另选取50例同期体检的健康儿童为正常对照组，比较两组外周血miR-17-5p表达情况。培养人肾足细胞株，分别转染含miR-17-5p反义寡核苷酸重组质粒（抑制组）、含无意义随机序列的对照载体（阴性对照组），未处理的人肾足细胞为空白组。比较各组细胞凋亡情况，以及转染后细胞miR-17-5p、ActA mRNA、Smads mRNA和相关蛋白表达情况。结果 NS组外周血miR-17-5p水平高于正常对照组（P < 0.001）。与空白组和阴性对照组比较，抑制组细胞凋亡率、miR-17-5p相对表达量更低，ActA、Smad2、Smad3三者的mRNA及蛋白相对表达量更高（P < 0.001）。结论 miR-17-5p在小儿NS外周血的含量升高，低表达miR-17-5p能抑制人肾足细胞的凋亡，其机制可能与上调ActA、Smad2、Smad3三者的mRNA及蛋白表达有关。

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	张延蕊
	武艺飞
	王慧
	林新梅
	张晓敏

关键词 ：肾病综合征, 微小RNA-17-5p, 激活素A, 人肾足细胞, 儿童

Abstract：Objective To study the role of microRNA-17-5p (miR-17-5p) in the pathogenesis of pediatric nephrotic syndrome (NS) and its effect on renal podocyte apoptosis via the activin A (ActA)/Smads pathway. Methods An analysis was performed on 55 children with NS (NS group) who were admitted from March 2018 to March 2019. Fifty healthy children who underwent physical examination during the same period of time were enrolled as the control group. The mRNA expression of miR-17-5p in peripheral blood was measured and compared between the two groups. Human renal podocytes were transfected with antisense oligonucleotide recombinant plasmid containing miR-17-5p (inhibition group) or control vector containing nonsense random sequence (negative control group), and untreated human renal podocytes were used as the blank group. These groups were compared in terms of cell apoptosis and the mRNA and protein expression of miR-17-5p, ActA, and Smads after transfection. Results The NS group had a significantly higher level of miR-17-5p in peripheral blood than the control group (P < 0.001). Compared with the blank and negative control groups, the inhibition group had significantly lower apoptosis rate and relative mRNA expression of miR-17-5p and significantly higher relative mRNA and protein expression of ActA, Smad2, and Smad3 (P < 0.001). Conclusions There is an increase in the content of miR-17-5p in peripheral blood in children with NS. Low expression of miR-17-5p can inhibit the apoptosis of human renal podocytes, which may be associated with the upregulation of the mRNA and protein expression of ActA, Smad2 and Smad3.

Key words： Nephrotic syndrome MicroRNA-17-5p Activin A Human renal podocyte Child

收稿日期: 2019-03-31

基金资助:2017年度山东省医药卫生科技发展计划（2017WS689）。

作者简介: 张延蕊,女,硕士,主治医师。Email:kz_2yw@163.com。

引用本文:

张延蕊,武艺飞,王慧等. 微小RNA-17-5p在小儿肾病综合征发病中的作用及其机制研究[J]. 中国当代儿科杂志, 2020, 22(9): 958-963.

ZHANG Yan-Rui,WU Yi-Fei,WANG Hui et al. Role of microRNA-17-5p in the pathogenesis of pediatric nephrotic syndrome and related mechanisms[J]. CJCP, 2020, 22(9): 958-963.

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http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2003329 或 http://www.zgddek.com/CN/Y2020/V22/I9/958

[1]	Sun W, Yu J, Zeng GL, et al. Preliminary research on syndrome types of Chinese medicine in children with primary nephrotic syndrome[J]. Chin J Integr Med, 2018, 24(8):579-583.
[2]	Mohanapriya CD, Vettriselvi V, Nammalwar BR, et al. Novel variations in NPHS1 gene in children of South Indian population and its association with primary nephrotic syndrome[J]. J Cell Biochem, 2018, 119(12):10143-10150.
[3]	Sanajou D, Ghorbani Haghjo A, Argani H, et al. FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats[J]. J Physiol Biochem, 2018, 74(3):467-478.
[4]	Tabatabaeifar M, Wlodkowski T, Simic I, et al. An inducible mouse model of podocin-mutation-related nephrotic syndrome[J]. PLoS One, 2017, 12(10):e0186574.
[5]	Guo H, Shen X, Xu Y, et al. The effect of activin A on signal transduction pathways in PC12 cells subjected to oxygen and glucose deprivation[J]. Int J Mol Med, 2014, 33(1):135-141.
[6]	杨凤英. 糖尿病肾病潜在调控机制的生物信息学分析[D]. 武汉:华中科技大学, 2018.
[7]	中华医学会儿科学分会肾脏病学组. 小儿肾小球疾病的临床分类、诊断及治疗[J]. 中华儿科杂志, 2001, 39(12):746-749.
[8]	Fujinaga S, Nishino T. Favorable renal outcome of Japanese children with severe IgA nephropathy with nephrotic syndrome[J]. Indian Pediatr, 2018, 55(7):605-607.
[9]	Youssef DM, Abd Al-Atif AM, El-Khateeb SSH, et al. Evaluation of interleukin-18 in children with steroid-sensitive nephrotic syndrome before and after using levamisole[J]. Saudi J Kidney Dis Transpl, 2018, 29(3):591-597.
[10]	杨莹, 范秋灵, 李露露, 等. miRNA-148b靶向AMPKα1通过氧化应激介导高糖诱导的人肾小管上皮细胞凋亡[J]. 中华肾脏病杂志, 2019, 35(1):43-47.
[11]	Hao J, Wei Q, Mei S, et al. Induction of microRNA-17-5p by p53 protects against renal ischemia-reperfusion injury by targeting death receptor 6[J]. Kidney Int, 2017, 91(1):106-118.
[12]	赵鹏南, 罗桂平, 姜云瀚, 等. MiR-17-5p调控STAT3信号通路在心肌慢性缺氧适应中意义的研究[J]. 第三军医大学学报, 2016, 38(6):589-594.
[13]	Zhou M, Cai J, Tang Y, et al. MiR-17-92 cluster is a novel regulatory gene of cardiac ischemic/reperfusion injury[J]. Med Hypotheses, 2013, 81(1):108-110.
[14]	任玮, 余宏川, 王萍, 等. miR-17-5p诱导小鼠肾足细胞系凋亡[J]. 基础医学与临床, 2019, 39(7):973-977.
[15]	Kiagiadaki F, Kampa M, Voumvouraki A, et al. Activin-A causes Hepatic stellate cell activation via the induction of TNFα and TGFβ in Kupffer cells[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(3):891-899.
[16]	Zhu Q, Chang A, Xu A, et al. The regulatory protein SnoN antagonizes activin/Smad2 protein signaling and thereby promotes adipocyte differentiation and obesity in mice[J]. J Biol Chem, 2018, 293(36):14100-14111.
[17]	Liu YY, Shi Y, Liu Y, et al. Telomere shortening activates TGF-β/Smads signaling in lungs and enhances both lipopolysaccharide and bleomycin-induced pulmonary fibrosis[J]. Acta Pharmacol Sin, 2018, 39(11):1735-1745.
[18]	Yeh HW, Hsu EC, Lee SS, et al. PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis[J]. Nat Cell Biol, 2018, 20(4):479-491.
[19]	梅巧. 滋勒调经汤对大鼠卵巢颗粒细胞增殖和分泌的影响[D]. 南宁:广西中医药大学, 2016.
[20]	Mang J, Mei CL, Wang JQ, et al. Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells[J]. Molecules, 2013, 18(10):12977-12986.