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CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis

Xinyan Miao1, Yuexin Tian1, Lunbi Wu1

  • 1Department of Pathology; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University; Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, 050017, China.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|May 6, 2022
PubMed

Insights

Circular RNAs (circRNAs) like circRTN4 worsen lupus nephritis (LN) by promoting cell dysfunction. Targeting circRTN4 offers a potential therapeutic strategy for this kidney disease.

Area of Science:

  • Molecular Biology
  • Immunology
  • Nephrology

Background:

  • Circular RNAs (circRNAs) regulate gene expression and are implicated in renal diseases.
  • The specific role of circRNAs in lupus nephritis (LN) progression remains unclear.

Purpose of the Study:

  • To elucidate the role and mechanism of circRNAs in lupus nephritis.
  • To identify circRNAs as potential biomarkers and therapeutic targets for LN.

Main Methods:

  • Investigated hsa_circ_0054595 (circRTN4) expression in human renal mesangial cells (HRMCs) and LN patients.
  • Examined the interaction between circRTN4, miR-513a-5p, and fibronectin (FN).
  • Utilized mouse models (MRL/lpr and BALB/c) and exosomal transfer studies to assess circRTN4 function.
  • Analyzed circRTN4 levels in peripheral blood mononuclear cells and kidney tissues of LN patients.

Main Results:

  • circRTN4 was upregulated in HRMCs and associated with increased FN expression via miR-513a-5p.
  • Exosomal circRTN4 promoted HRMC proliferation and extracellular matrix deposition.
  • circRTN4 knockdown alleviated renal damage in mouse models of LN.
  • Elevated circRTN4 levels were detected in LN patients' blood and kidney tissues.

Conclusions:

  • circRTN4 exacerbates mesangial cell dysfunction in LN by activating the miR-513a-5p/FN axis.
  • circRTN4 serves as a potential biomarker for LN detection.
  • circRTN4 represents a novel therapeutic target for lupus nephritis.

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