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.
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.
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.
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.
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.
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.
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.
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.
