Evidence map›Paper›PMID 40040710›Full record

ArticleFrontiers in immunology2025

Claudin-2 enhances human antibody-mediated complement-dependent cytotoxicity of porcine endothelial cells by modulating antibody binding and complement activation.

Weilong Li, Fang Yang, Dexin Yang, Zhuoheng Song, Zigan Xu, Jinmei Wu, Yanmei Li, Zixi Chen, Peishan Chen, Yeye Yu and 5 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Weilong Li *Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Fang Yang *Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Dexin YangDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Zhuoheng SongDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Zigan XuDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Jinmei WuDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Yanmei LiDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Zixi ChenDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Peishan ChenDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Yeye YuDepartment of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Ting XieDepartment of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Cuishan YangDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Liying ZhouDepartment of obstetrics, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for diagnosis and treatment of chronic kidney disease, Shenzhen, Guangdong, China.
Shaodong LuanDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.
Hanchao GaoDepartment of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen Longhua District Key Laboratory for Diagnosis and Treatment of Chronic Kidney Disease, Shenzhen, Guangdong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Immune rejection represents a significant barrier to transplantation, especially in the context of xenotransplantation. Endothelial cells (ECs) derived from pigs serve as the initial barrier against the human immune system in xenotransplantation. Tight junction proteins are essential components of endothelial cell tight junctions; however, their role in xenotransplantation has been less thoroughly investigated. Claudin-2, a key tight junction protein, was investigated here for its role in human antibody-mediated complement-dependent cytotoxicity (CDC). Methods: Using an Results: The loss of Claudin-2 protected PAECs and PIECs from human antibody-mediated CDC, while the overexpression of Claudin-2 enhanced the cytotoxicity in PAECs and PIECs within the same model. Unexpectedly, the loss or overexpression of Claudin-2 did not influence the mRNA expression levels of complement regulators (CD46, CD55, CD59, Factor H, and Factor I). Importantly, the loss of Claudin-2 significantly decreased the deposition of the C5b-9 complex, commonly referred to as the membrane attack complex (MAC), whereas the overexpression of Claudin-2 enhanced the deposition of the C5b-9 complex, indicating that Claudin-2 facilitates complement activation. Furthermore, the loss of Claudin-2 resulted in a decrease in the deposition of C3c and C9 on PIECs. Moreover, Claudin-2 enhanced human antibody binding to porcine ECs, as evidenced by increased IgG and IgM binding. Conclusion: Our findings indicate that Claudin-2 enhances the cytotoxicity of porcine ECs through modulating antibody binding and complement activation. The deficient of Claudin-2 in genetically modified pigs is likely to protect porcine ECs and enhance xenograft survival in pig-to-human organ or tissue xenotransplantation.

Indexed as

AntibodiesClaudin-2Complement C3cComplement Membrane Attack ComplexEndothelial CellsAnimalsApoptosisCell Membrane PermeabilityCell ProliferationCell ShapeCytotoxicity Tests, ImmunologicGene Expression RegulationHumansRNA, Small InterferingSwineAntibodiesClaudin-2Complement C3cComplement Membrane Attack ComplexRNA, Small InterferingantibodyClaudin-2complementimmune rejectioninflammationPAECsPIECsxenotransplantation

Identifiers

PMID40040710
PMCPMC11876394

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.