IL‑17 aggravates renal injury by promoting podocyte injury in children with primary nephrotic syndrome

Zhai,Shubo; Sun,Baichao; Zhang,Yan; Zhao,Lengyue; Zhang,Li

doi:10.3892/etm.2020.8698

IL‑17 aggravates renal injury by promoting podocyte injury in children with primary nephrotic syndrome

Authors:
- Shubo Zhai
- Baichao Sun
- Yan Zhang
- Lengyue Zhao
- Li Zhang
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Affiliations: Department of Pediatric Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: April 29, 2020 https://doi.org/10.3892/etm.2020.8698
Pages: 409-417
Copyright: © Zhai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Primary nephrotic syndrome (PNS) is the most common chronic kidney disease in childhood, where podocyte injury is a key factor in the occurrence of kidney disease. In the present study, the expression of IL‑17 in renal tissues of patients with PNS and its relationship with podocyte injury were examined. Reverse transcription‑quantitative PCR (RT‑qPCR), western blot analysis and immunochemistry were used to measure the expression of IL‑17 in renal biopsies of patients with ONS, including 9 patients with minimal change nephrotic syndrome (MCNS), 15 patients with mesangial proliferative glomerulonephritis (MsPGN) and 9 patients with focal segmental glomerulosclerosis (FSGS), in addition to 15 normal kidney tissues. IL‑17 was found to be highly expressed in the renal tissues from patients with PNS, with the highest expression levels found in tissues from patients with FSGS and the lowest in those from MCNS. A negative correlation was observed between the levels of IL‑17 mRNA and PCX mRNA in renal tissues, whereas a positive correlation between IL‑17 mRNA levels and the number of urinary podocytes in patients with PNS was found. In vitro, IL‑17 induced podocyte apoptosis and reduced the expression of markers associated with podocytes, including Wilm's tumor 1, nephrin, synaptopodin and podocalyxin, whilst increasing the levels of Fas, Fas ligand (FasL), active‑caspase‑8, active‑caspase‑3 and phosphorylated‑p65. However, treatment with helenalin, a NF‑κB inhibitor, decreased p65 phosphorylation, attenuated IL‑17‑induced podocyte apoptosis and suppressed the IL‑17‑activated Fas/FasL/caspase‑8/caspase‑3 apoptotic pathway. Taken together, these observations suggest that IL‑17 was highly expressed in renal tissues from patients with PNS, where it induced podocyte apoptosis by activating the Fas/FasL/caspase‑8/caspase‑3 apoptotic pathway in a NF‑κB‑dependent manner.

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