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The protective function of miR-378 in the ischemia–reperfusion injury during renal transplantation and subsequent interstitial fibrosis of the renal allograft

  • Nephrology - Original Paper
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Abstract

Survival time of kidney transplant patients is primarily threatened by chronic allograft dysfunction (CAD), whose typical feature is interstitial fibrosis and tubular atrophy (IF/TA). CAD could be caused by ischemia–reperfusion injury (IRI) during renal transplantation. MiR-378 is correlated with multiple kidney diseases and implicated in CAD. To clarify the underlying mechanism of miR-378 on renal allograft, we utilize renal unilateral IRI mice and H/R NRK52E cells. To evaluate the acute tubular damage, we determined the apoptotic rate by TUNEL assay and examined mice kidney sections of H&E staining 1 day after IRI. To assess the chronic renal interstitial inflammation and fibrosis, we detected the infiltration rates of CD45R+ leukocytes and Ly6b+ neutrophils by immunohistochemistry, examined mice kidney sections of picrosirius staining and measured the mRNA level of Col1a1 14 days after IRI. To investigate the H/R injury of NRK52E cells, MTT assay was performed to detect cell viability, TUNEL assay was performed to determine apoptotic rate and luciferase reporter assay was carried out to demonstrate the potential target of miR-378. Moreover, we determined the levels of miR-378 of renal allograft biopsies in healthy patients and patients diagnosed with IF/TA. We found agomir-378 treatment significantly reduced the apoptotic rate and tubular damage scores assessed by H&E staining 1 day after IRI. Agomir-378 treatment also decreased infiltration rates of both CD45R+ leukocytes and Ly6b+ neutrophils and fibrosis examined by picrosirius staining and by the mRNA level of Col1a1 14 days after IRI. Experiments in vitro revealed that miR-378 increased cell viability and decreased apoptotic rate of NRK52E cells subjected to H/R. Additionally, luciferase reporter assay confirmed that caspase 3 was targeted by miR-378 directly. Furthermore, we found the levels of miR-378 were significantly lower in renal allografts of patients with IF/TA than those of healthy controls. Taken together, we have found that miR-378 has potential protective effects on renal allografts to prevent IRI during kidney transplantation and following IF/TA of renal allografts.

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Authors and Affiliations

  1. Department of Kidney Transplant, Yiyang Central Hospital, No.118 Kangfu North Road, Yiyang, 413000, Hunan, China

    Lie Xiong, ShouNing Ding & Tie Yang

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  1. Lie Xiong
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  2. ShouNing Ding
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  3. Tie Yang
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LX designed the study, conducted most of the experiments and wrote the manuscript; SD and TY conducted the experiments and analyzed the data.

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Correspondence to Lie Xiong.

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Xiong, L., Ding, S. & Yang, T. The protective function of miR-378 in the ischemia–reperfusion injury during renal transplantation and subsequent interstitial fibrosis of the renal allograft. Int Urol Nephrol 52, 1791–1800 (2020). https://doi.org/10.1007/s11255-020-02540-9

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  • DOI: https://doi.org/10.1007/s11255-020-02540-9

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