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LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes

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Abstract

Diabetic nephropathy (DN), characterized by glomerular injury, is a common complication of both type 1 and type 2 diabetes, accompanied by massive proteinuria. Podocytes are reported to play pivotal roles in maintaining the glomerular filtration barrier. In addition, the expression of long non-coding RNAs (lncRNAs) ANRIL was upregulated in type 2 diabetes patients. Hence, the aim of this study was to investigate the underlying mechanisms implicated the role of LncRNA ANRIL in podocyte injury in DN. The concentration of inflammatory cytokines was quantified by the corresponding enzyme-linked immunosorbent assay (ELISA) kits. The mRNA levels of the target gene were determined by reverse transcription and real-time quantitative PCR (RT-qPCR). The expressions of proteins were evaluated by Western blot. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) level were measured by corresponding commercial kits. Finally, the apoptosis of podocytes was analyzed by TUNEL assay. In our study, LncRNA ANRIL was highly expressed in high glucose (HG)-induced podocytes. Moreover, LncRNA ANRIL silencing attenuated HG-induced inflammation, oxidative stress, and apoptosis and induced MME overexpression in podocytes. Interestingly, MME knockdown abolished the suppressive effect of LncRNA ANRIL silencing on HG-induced inflammation, oxidative stress, and apoptosis in podocytes. LncRNA ANRIL silencing alleviates HG-induced inflammation, oxidative stress, and apoptosis via upregulation of MME in podocytes. Hence, LncRNA ANRIL may be a novel and effective target to ameliorate podocyte injury in DN.

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Abbreviations

DN:

diabetic nephropathy

ESRD:

end-stage renal disease

LncRNAs:

long non-coding RNAs

TNF:

tumor necrosis factor

IL:

interleukin

LDH:

lactate dehydrogenase

SOD:

superoxide dismutase

MDA:

malondialdehyde

HG:

high glucose

MME:

membrane metallo-endopeptidase

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Authors and Affiliations

  1. Department of Endocrinology, The Second People’s Hospital of Jingzhou City, Jingzhou, City, 434000, Hubei Province, People’s Republic of China

    Ruiyu Cai

  2. Department of Nephrology, Jiangsu Province Geriatric Hospital, Geriatric Hospital of Nanjing Medical University, No. 65 Jiangsu Road, Nanjing City, 210009, Jiangsu Province, People’s Republic of China

    Juanjuan Jiang

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R.C. and J.J. participated in the conception of the study and writing of the manuscript. All of the authors have read and approved the final manuscript.

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Correspondence to Juanjuan Jiang.

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Cai, R., Jiang, J. LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes. Inflammation 43, 2147–2155 (2020). https://doi.org/10.1007/s10753-020-01282-1

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