Iranian Journal of Immunology

Angiopoietin-like 4 (ANGPTL4) Suppression Ameliorates Lupus Nephritis in MRL/lpr Mice by Inactivating NLRP3 Inflammasome and Inhibiting Inflammatory Response

Document Type : Original Article

Authors

Dan Luo 1
Jun Li 1
Manli Hu 1
You Wang 1
Pei Pi 1
Min Ning 1
Jun Wu 2

1 Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China.

2 Department of Endocrine, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China.

https://doi.org/10.22034/iji.2023.97942.2541
Abstract
Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.
Objective: To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.
Methods: MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.
Results: The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.
Conclusion: ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.

Keywords

ANGPTL4
Inflammation
Lupus Nephritis
NLRP3 Inflammasome
Systemic Lupus Erythematosus
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Iranian Journal of Immunology
Volume 20, Issue 3
Summer 2023
Pages 316-326

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