---
title: "C5a-C5aR1 axis drives NET formation in SARS-CoV-2 N protein–mediated acute kidney injury"
id: "pubmed-42468179"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42468179"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42468179/"
doi: "10.1016/j.bbrc.2026.154305"
published_at: "2026-09-17T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# C5a-C5aR1 axis drives NET formation in SARS-CoV-2 N protein–mediated acute kidney injury
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42468179
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42468179/)
- **DOI:** [10.1016/j.bbrc.2026.154305](https://doi.org/10.1016%2Fj.bbrc.2026.154305)
- **Published At:** 2026-09-17T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study investigated mechanisms of COVID-19–associated acute kidney injury (AKI) using a mouse model with kidney-specific expression of the SARS-CoV-2 nucleocapsid (**N protein**). - Kidney-specific N protein expression was achieved by ultrasound-microbubble-mediated gene delivery; the model produced neutrophil infiltration and **neutrophil extracellular trap (NET)** formation in the kidney. - The authors measured complement activation and found elevated serum **C5a** and increased renal **C5aR1** expression associated with N protein expression. - Interventions included a pharmacologic **C5aR1 inhibitor (DF2593A)** and **DNase I (Pulmozyme)** to degrade NETs; both were applied in the AKI model. - Inhibition of C5aR1 or degradation of NETs reduced renal tubular injury and lowered markers of renal dysfunction: serum creatinine, blood urea nitrogen (BUN), and kidney injury molecule-1 (**KIM-1**). - The data are interpreted to indicate that activation of the **C5a-C5aR1 axis** promotes NET formation and contributes to N protein–mediated AKI. - The authors propose that targeting the C5a-C5aR1 axis or NETs may represent a potential therapeutic approach for COVID-19–associated renal injury. - The report used an animal disease model; details such as sample sizes, timing, statistical measures, and full experimental protocols were not reported in the abstract. - Authors declared no conflicts of interest.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 16. # C5a-C5aR1 axis activation drives neutrophil extracellular trap formation in SARS-CoV-2 N protein-mediated acute kidney injury [Cuilan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42468179)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-1 "The First Affiliated Hospital of Hebei North University, Hebei, China. Electronic address: 15612301085@163.com."), [Ziyi Yan](https://pubmed.ncbi.nlm.nih.gov/?term=Yan+Z&cauthor_id=42468179)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-2 "Hebei North University, Hebei, China."), [Ziyi Tao](https://pubmed.ncbi.nlm.nih.gov/?term=Tao+Z&cauthor_id=42468179)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-2 "Hebei North University, Hebei, China."), [Wen Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+W&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Xiaoli Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+X&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Linlin Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Shengjun Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+S&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#full-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China.") Affiliations Expand ### Affiliations * 1 The First Affiliated Hospital of Hebei North University, Hebei, China. Electronic address: 15612301085@163.com. * 2 Hebei North University, Hebei, China. * 3 The First Affiliated Hospital of Hebei North University, Hebei, China. * PMID: **42468179** * DOI: [ 10.1016/j.bbrc.2026.154305 ](https://doi.org/10.1016/j.bbrc.2026.154305) Item in Clipboard # C5a-C5aR1 axis activation drives neutrophil extracellular trap formation in SARS-CoV-2 N protein-mediated acute kidney injury Cuilan Liu et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42468179/) . 2026 Sep 17:831:154305. doi: 10.1016/j.bbrc.2026.154305. Epub 2026 Jul 16. ### Authors [Cuilan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42468179)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-1 "The First Affiliated Hospital of Hebei North University, Hebei, China. Electronic address: 15612301085@163.com."), [Ziyi Yan](https://pubmed.ncbi.nlm.nih.gov/?term=Yan+Z&cauthor_id=42468179)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-2 "Hebei North University, Hebei, China."), [Ziyi Tao](https://pubmed.ncbi.nlm.nih.gov/?term=Tao+Z&cauthor_id=42468179)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-2 "Hebei North University, Hebei, China."), [Wen Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+W&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Xiaoli Han](https://pubmed.ncbi.nlm.nih.gov/?term=Han+X&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Linlin Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China."), [Shengjun Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+S&cauthor_id=42468179)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42468179/#short-view-affiliation-3 "The First Affiliated Hospital of Hebei North University, Hebei, China.") ### Affiliations * 1 The First Affiliated Hospital of Hebei North University, Hebei, China. Electronic address: 15612301085@163.com. * 2 Hebei North University, Hebei, China. * 3 The First Affiliated Hospital of Hebei North University, Hebei, China. * PMID: **42468179** * DOI: [ 10.1016/j.bbrc.2026.154305 ](https://doi.org/10.1016/j.bbrc.2026.154305) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract The mechanism of COVID-19-associated acute kidney injury (AKI) remains incompletely understood. This study aimed to investigate the regulatory role of the C5a-C5aR1 axis in neutrophil extracellular trap (NET) formation in SARS-CoV-2 nucleocapsid (N) protein-induced AKI. An AKI mouse model with kidney-specific N protein expression was established using ultrasound-microbubble-mediated technology, and interventions with the C5aR1 inhibitor DF2593A or DNase I (Pulmozyme) were administered to detect renal neutrophil infiltration, NET deposition, C5a-C5aR1 expression, and renal function indices. The results showed that N protein expression significantly induced neutrophil infiltration and NET formation, accompanied by elevated serum C5a and upregulated C5aR1. Inhibition of C5aR1 or degradation of NETs effectively attenuated renal tubular injury and decreased serum creatinine, blood urea nitrogen, and kidney injury molecule-1 (KIM-1) levels. In conclusion, activation of the C5a-C5aR1 axis contributes to N protein-mediated AKI by driving NET formation, and targeting this axis may provide a potential therapeutic strategy for COVID-19-associated renal injury. **Keywords:** Acute kidney injury; C5a-C5aR1 axis; Complement activation; Neutrophil extracellular traps; SARS-CoV-2 N protein. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest All authors declare no conflicts of interest. ## Similar articles * [ HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury. ](https://pubmed.ncbi.nlm.nih.gov/39850900/) Zhu L, Zheng Q, Liu X, Ding H, Ma M, Bao J, Cai Y, Cao C.Zhu L, et al.Front Immunol. 2025 Jan 9;15:1475543. doi: 10.3389/fimmu.2024.1475543. eCollection 2024.Front Immunol. 2025.PMID: 39850900Free PMC article. * [ SARS-CoV-2 N protein induces hypokalemia in acute kidney injury mice via ENaC-dependent mechanism. ](https://pubmed.ncbi.nlm.nih.gov/40336195/) Zhang DD, Liu Y, Wang W, Wu W, Chen J, Wan L, Wu L, Huang XR, Lan HY, Yu X.Zhang DD, et al.Mol Ther. 2025 Aug 6;33(8):3778-3788. doi: 10.1016/j.ymthe.2025.04.043. Epub 2025 May 6.Mol Ther. 2025.PMID: 40336195Free PMC article. * [ Complement component 5a receptor 1 and leukotriene B4 receptor 1 regulate neutrophil extracellular trap (NET) formation through Rap1a/B-Raf/ERK signaling pathway and their deficiency in term low birth weight newborns leads to deficient NETosis. ](https://pubmed.ncbi.nlm.nih.gov/39303536/) Das D, Thacker H, Priya K, Jain M, Singh S, Rai G.Das D, et al.Int Immunopharmacol. 2024 Dec 5;142(Pt B):113165. doi: 10.1016/j.intimp.2024.113165. Epub 2024 Sep 19.Int Immunopharmacol. 2024.PMID: 39303536 * [ The critical role of C5a as an initiator of neutrophil-mediated autoimmune inflammation of the joint and skin. ](https://pubmed.ncbi.nlm.nih.gov/29602515/) Sadik CD, Miyabe Y, Sezin T, Luster AD.Sadik CD, et al.Semin Immunol. 2018 Jun;37:21-29. doi: 10.1016/j.smim.2018.03.002. Epub 2018 Mar 27.Semin Immunol. 2018.PMID: 29602515Review. * [ Complement in acute kidney injury: a convergent pathogenic pathway in multifactorial renal damage. ](https://pubmed.ncbi.nlm.nih.gov/42253993/) Yi D, Yang R, Guo Y, Zhou H, Luan J.Yi D, et al.Front Immunol. 2026 May 22;17:1840335. doi: 10.3389/fimmu.2026.1840335. eCollection 2026.Front Immunol. 2026.PMID: 42253993Free PMC article.Review. 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