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Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis

Author

Listed:
  • Qiulun Lu

    (Georgia State University)

  • Zejun Ma

    (Georgia State University
    Tianjin Medical University)

  • Ye Ding

    (Georgia State University)

  • Tatiana Bedarida

    (Georgia State University)

  • Liming Chen

    (Tianjin Medical University)

  • Zhonglin Xie

    (Georgia State University)

  • Ping Song

    (Georgia State University)

  • Ming-Hui Zou

    (Georgia State University)

Abstract

Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-κB (NF-κB)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-κB/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-κB/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis.

Suggested Citation

  • Qiulun Lu & Zejun Ma & Ye Ding & Tatiana Bedarida & Liming Chen & Zhonglin Xie & Ping Song & Ming-Hui Zou, 2019. "Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10116-0
    DOI: 10.1038/s41467-019-10116-0
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    Cited by:

    1. Alexandra Braun & Dimitar Evdokimov & Johanna Frank & Claudia Sommer & Nurcan Üçeyler, 2020. "MiR103a-3p and miR107 are related to adaptive coping in a cluster of fibromyalgia patients," PLOS ONE, Public Library of Science, vol. 15(9), pages 1-12, September.

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