Local renal complement activation mediates immune kidney injury by inducing endothelin-1 signalling and inflammation in trichloroethylene-sensitised mice.

Wang, G; Zhang, J; Dai, Y; Xu, Q; Zhu, Q

Local renal complement activation mediates immune kidney injury by inducing endothelin-1 signalling and inflammation in trichloroethylene-sensitised mice.

Wang, G

Zhang, J Dai, Y Xu, Q Zhu, Q

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Publisher:: ELSEVIER IRELAND LTD
Publication Type:: Journal Article
Citation:: Toxicology letters, 2020, 333, pp. 130-139
Issue Date:: 2020-10

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Field	Value	Language
dc.contributor.author	Wang, G https://orcid.org/0000-0003-4295-8578
dc.contributor.author	Zhang, J
dc.contributor.author	Dai, Y
dc.contributor.author	Xu, Q
dc.contributor.author	Zhu, Q
dc.date.accessioned	2021-06-09T23:53:09Z
dc.date.available	2020-07-31
dc.date.available	2021-06-09T23:53:09Z
dc.date.issued	2020-10
dc.identifier.citation	Toxicology letters, 2020, 333, pp. 130-139
dc.identifier.issn	0378-4274
dc.identifier.issn	1879-3169
dc.identifier.uri	http://hdl.handle.net/10453/149476
dc.description.abstract	Trichloroethylene (TCE) is a widely used industrial solvent that causes trichloroethylene hypersensitivity syndrome (THS) with multi-system damage, including kidney injury. Clinical studies have shown that the complement system is important for TCE-induced kidney injury. Our previous study found excessive deposition of complement C3, mainly on the glomerulus, indicating that local renal complement is activated after TCE sensitisation. However, whether local renal complement activation mediates TCE-induced immune kidney injury and the underlying mechanisms remain unknown. Therefore, we established a TCE percutaneous sensitisation BALB/c mouse model to explore the mechanisms by pretreating with or without the complement activation antagonist, cathepsin L inhibitor (CatLi). As expected, more C3 and C3a were detected mainly on glomerulus of TCE positive sensitisation (TCE<sup>+</sup>) mice. Renal dysfunction and pathological damage were also clearly observed in TCE<sup>+</sup> mice. Moreover, the mRNA and protein expression of ET-1 increased significantly with local renal complement activation after TCE sensitisation, leading to cytokines release and inflammation. In addition, activation of p38MAPK and NF-κBp65 pathways were detected in kidneys of TCE<sup>+</sup> mice, and CatLi pretreatment decreased these changes through complement activation antagonisation. Our research uncovered a novel role of local renal complement activation during immune kidney injury after TCE sensitisation through induction of ET-1 signalling and inflammation.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER IRELAND LTD
dc.relation.ispartof	Toxicology letters
dc.relation.isbasedon	10.1016/j.toxlet.2020.07.036
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0502 Environmental Science and Management, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Toxicology
dc.subject.mesh	Animals
dc.subject.mesh	Complement Activation
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endothelin-1
dc.subject.mesh	Female
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Inflammation
dc.subject.mesh	Kidney
dc.subject.mesh	MAP Kinase Signaling System
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	NF-kappa B
dc.subject.mesh	Renal Insufficiency
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Trichloroethylene
dc.subject.mesh	Kidney
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Inflammation
dc.subject.mesh	Trichloroethylene
dc.subject.mesh	Endothelin-1
dc.subject.mesh	NF-kappa B
dc.subject.mesh	Signal Transduction
dc.subject.mesh	MAP Kinase Signaling System
dc.subject.mesh	Complement Activation
dc.subject.mesh	Female
dc.subject.mesh	Renal Insufficiency
dc.subject.mesh	Animals
dc.subject.mesh	Complement Activation
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endothelin-1
dc.subject.mesh	Female
dc.subject.mesh	Hypersensitivity
dc.subject.mesh	Inflammation
dc.subject.mesh	Kidney
dc.subject.mesh	MAP Kinase Signaling System
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	NF-kappa B
dc.subject.mesh	Renal Insufficiency
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Trichloroethylene
dc.title	Local renal complement activation mediates immune kidney injury by inducing endothelin-1 signalling and inflammation in trichloroethylene-sensitised mice.
dc.type	Journal Article
utslib.citation.volume	333
utslib.location.activity	Netherlands
utslib.for	0502 Environmental Science and Management
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2021-06-09T23:53:05Z
pubs.publication-status	Published
pubs.volume	333

Abstract:

Trichloroethylene (TCE) is a widely used industrial solvent that causes trichloroethylene hypersensitivity syndrome (THS) with multi-system damage, including kidney injury. Clinical studies have shown that the complement system is important for TCE-induced kidney injury. Our previous study found excessive deposition of complement C3, mainly on the glomerulus, indicating that local renal complement is activated after TCE sensitisation. However, whether local renal complement activation mediates TCE-induced immune kidney injury and the underlying mechanisms remain unknown. Therefore, we established a TCE percutaneous sensitisation BALB/c mouse model to explore the mechanisms by pretreating with or without the complement activation antagonist, cathepsin L inhibitor (CatLi). As expected, more C3 and C3a were detected mainly on glomerulus of TCE positive sensitisation (TCE⁺) mice. Renal dysfunction and pathological damage were also clearly observed in TCE⁺ mice. Moreover, the mRNA and protein expression of ET-1 increased significantly with local renal complement activation after TCE sensitisation, leading to cytokines release and inflammation. In addition, activation of p38MAPK and NF-κBp65 pathways were detected in kidneys of TCE⁺ mice, and CatLi pretreatment decreased these changes through complement activation antagonisation. Our research uncovered a novel role of local renal complement activation during immune kidney injury after TCE sensitisation through induction of ET-1 signalling and inflammation.

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http://hdl.handle.net/10453/149476