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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 51, 2022 - Issue 5
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Research Article

LncRNA CRNDE Exacerbates IgA Nephropathy Progression by Promoting NLRP3 Inflammasome Activation in Macrophages

, , , , , , , , , & show all
Pages 1515-1527 | Published online: 07 Nov 2021
 

ABSTRACT

Background

Activation of NLRP3 inflammasome in macrophages contributes greatly to IgA nephropathy (IgAN) progression. This study intended to investigate the underlying mechanism of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in the development of IgAN.

Methods

We examined the expression levels of colorectal neoplasia differentially expressed (CRNDE), NLRP3 inflammasome-related proteins in peripheral blood mononuclear cells (PBMCs) and J774A.1 cells and detected inflammatory cytokine levels in the serum of IgAN patients and cell supernatants of in vitro IgAN model. RNA pull-down and RNA immunoprecipitation (RIP) experiments were conducted to evaluate the interaction between CRNDE and NLRP3. Then, the ubiquitin level of NLRP3 and its binding ability to TRIM family member 31 (TRIM31) were determined.

Results

Compared with the control group, the expressions of CRNDE and NLRP3 inflammasome-related proteins in PBMCs and J774A.1 cells and levels of IL-1β, TNF-α and IL-12 in serum of IgAN patients and cell supernatants of IgA-IC-induced J774A.1 cells were all increased. CRNDE silencing down-regulated NLRP3 inflammasome-related proteins and the levels of IL-1β, TNF-α and IL-12 in cell supernatants, while NLRP3 overexpression reversed these effects. Additionally, CRNDE could interact with NLRP3 and promote NLRP3 expression. Furthermore, inhibition of CRNDE reduced NLRP3 protein level and promoted TRIM31-mediated NLRP3 ubiquitination and degradation.

Conclusion

CRNDE exacerbates IgA nephropathy progression through restraining ubiquitination and degradation of NLRP3 and facilitating NLRP3 inflammasome activation in macrophages.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [No. 2020358611], Wenzhou Science & Technology Bureau, [No. Y20180499, No. Y20190063], Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation [No. 19331203], Natural Science Foundation of Zhejiang Province [No. GD19H070005], and Clinical Research Fund of Zhejiang Medical Association [No. 2017ZYC-A28].

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