Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury
The aberrant activation of the intracellular complement system is a significant characteristic of trichloroethylene (TCE) -induced immune kidney injury. However, the specific role of complement factor H (CFH) in this context remains unclear. This study investigates the involvement of CFH / serum amy...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325006712 |
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| author | Haibo Xie Bo Liang Jingyi Zhao Chen You Qirui Bai Rui Li Jian Chen Pengcheng Zhou Luolun Dong Ruixuan Cheng Jiaxiang Zhang Qixing Zhu |
| author_facet | Haibo Xie Bo Liang Jingyi Zhao Chen You Qirui Bai Rui Li Jian Chen Pengcheng Zhou Luolun Dong Ruixuan Cheng Jiaxiang Zhang Qixing Zhu |
| author_sort | Haibo Xie |
| collection | DOAJ |
| description | The aberrant activation of the intracellular complement system is a significant characteristic of trichloroethylene (TCE) -induced immune kidney injury. However, the specific role of complement factor H (CFH) in this context remains unclear. This study investigates the involvement of CFH / serum amyloid A (SAA1) signaling in TCE-induced immune kidney injury by employing a combination of in vitro experiments and TCE-sensitized mouse model. Proteomic analyses results revealed that TCE-sensitized positive mice exhibited significantly increased expression of acute-phase reactive proteins, abnormal activation of the complement system. The treatment with TNFα and IFNγ-neutralizing antibodies reduced renal vascular endothelial cell injury and kidney damage in TCE-sensitized mice, and the combined treatment of recombinant TNFα and IFNγ reduced CFH intracellular expression but increased extracellular secretion in human renal glomerular endothelial cells (HRGECs). CFH in HRGECs notably protected endothelial barrier function when stimulated by TNFα and IFNγ. Moreover, CFH deficiency can lead to increased SAA1, which interacts with Toll-like receptor-2 (TLR2) to activate nuclear factor-kappaB (NF-κB). This study revealed that the combination of TNFα and IFNγ influences renal vascular endothelial barrier function by regulating the expression and secretion of local CFH. The downregulated intracellular CFH also associated with the inflammatory response in TCE-induced immune kidney injury by regulating the SAA1/TLR2 pathway. |
| format | Article |
| id | doaj-art-14f2284e8bea4b74aa47c6f94b85045f |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-14f2284e8bea4b74aa47c6f94b85045f2025-08-20T03:13:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811833510.1016/j.ecoenv.2025.118335Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injuryHaibo Xie0Bo Liang1Jingyi Zhao2Chen You3Qirui Bai4Rui Li5Jian Chen6Pengcheng Zhou7Luolun Dong8Ruixuan Cheng9Jiaxiang Zhang10Qixing Zhu11Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, ChinaDepartment of Dermatology, the Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui 230032, China; Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Corresponding author at: Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China; Institute of Dermatology, Anhui Medical University, Hefei, Anhui 230032, China; Correspondence to: Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China.The aberrant activation of the intracellular complement system is a significant characteristic of trichloroethylene (TCE) -induced immune kidney injury. However, the specific role of complement factor H (CFH) in this context remains unclear. This study investigates the involvement of CFH / serum amyloid A (SAA1) signaling in TCE-induced immune kidney injury by employing a combination of in vitro experiments and TCE-sensitized mouse model. Proteomic analyses results revealed that TCE-sensitized positive mice exhibited significantly increased expression of acute-phase reactive proteins, abnormal activation of the complement system. The treatment with TNFα and IFNγ-neutralizing antibodies reduced renal vascular endothelial cell injury and kidney damage in TCE-sensitized mice, and the combined treatment of recombinant TNFα and IFNγ reduced CFH intracellular expression but increased extracellular secretion in human renal glomerular endothelial cells (HRGECs). CFH in HRGECs notably protected endothelial barrier function when stimulated by TNFα and IFNγ. Moreover, CFH deficiency can lead to increased SAA1, which interacts with Toll-like receptor-2 (TLR2) to activate nuclear factor-kappaB (NF-κB). This study revealed that the combination of TNFα and IFNγ influences renal vascular endothelial barrier function by regulating the expression and secretion of local CFH. The downregulated intracellular CFH also associated with the inflammatory response in TCE-induced immune kidney injury by regulating the SAA1/TLR2 pathway.http://www.sciencedirect.com/science/article/pii/S0147651325006712Endothelial cellsKidneyComplement factor HSerum amyloid ATrichloroethylene |
| spellingShingle | Haibo Xie Bo Liang Jingyi Zhao Chen You Qirui Bai Rui Li Jian Chen Pengcheng Zhou Luolun Dong Ruixuan Cheng Jiaxiang Zhang Qixing Zhu Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury Ecotoxicology and Environmental Safety Endothelial cells Kidney Complement factor H Serum amyloid A Trichloroethylene |
| title | Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury |
| title_full | Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury |
| title_fullStr | Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury |
| title_full_unstemmed | Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury |
| title_short | Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury |
| title_sort | target complement factor h serum amyloid a signaling in trichloroethylene induced immune kidney injury |
| topic | Endothelial cells Kidney Complement factor H Serum amyloid A Trichloroethylene |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325006712 |
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