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DC Field | Value | Language |
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dc.contributor.author | Ozols E. | en |
dc.contributor.author | Nikolic-Paterson D.J. | en |
dc.contributor.author | Ma F.Y. | en |
dc.contributor.author | Liles J.T. | en |
dc.contributor.author | Badal S.S. | en |
dc.contributor.author | Kanellis J. | en |
dc.contributor.author | Leong K.G. | en |
dc.date.accessioned | 2021-05-14T09:37:06Z | en |
dc.date.available | 2021-05-14T09:37:06Z | en |
dc.date.copyright | 2021 | en |
dc.date.created | 20210126 | en |
dc.date.issued | 2021-01-26 | en |
dc.identifier.citation | International Journal of Molecular Sciences. 22 (1) (pp 1-19), 2021. Article Number: 271. Date of Publication: 01 Jan 2021. | en |
dc.identifier.issn | 1661-6596 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/28557 | en |
dc.description.abstract | Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochon-drial-dependent cell death. This study investigated the therapeutic potential of a selective cyclo-philin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment signifi-cantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.Copyright © 2020 by the authors. | en |
dc.language | en | en |
dc.language | English | en |
dc.publisher | MDPI AG | en |
dc.relation.ispartof | International Journal of Molecular Sciences | en |
dc.title | Cyclophilin inhibition protects against experimental acute kidney injury and renal interstitial fibrosis. | en |
dc.type | Article | en |
dc.identifier.affiliation | Nephrology | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url= | - |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.3390/ijms22010271 | en |
dc.publisher.place | Switzerland | en |
dc.identifier.pubmedid | 33383945 [http://www.ncbi.nlm.nih.gov/pubmed/?term=33383945] | en |
dc.identifier.source | 2005695622 | en |
dc.identifier.institution | (Leong, Ozols, Kanellis, Nikolic-Paterson, Ma) Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia (Leong, Ozols, Kanellis, Nikolic-Paterson, Ma) Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia (Badal, Liles) Gilead Sciences, Foster City, CA 94404, United States | en |
dc.description.address | D.J. Nikolic-Paterson, Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia. E-mail: david.nikolic-paterson@monash.edu D.J. Nikolic-Paterson, Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia. E-mail: david.nikolic-paterson@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2021 Elsevier B.V., All rights reserved. | en |
dc.subect.keywords | Acute kidney injury Cell death Chronic kidney disease Cyclophilin Inflammation Mac-rophage Neutrophil Renal fibrosis | en |
dc.identifier.authoremail | Leong K.G.; khaigeneleong@gmail.com Ozols E.; elyce.ozols@monash.edu Kanellis J.; john.kanellis@monash.edu Nikolic-Paterson D.J.; david.nikolic-paterson@monash.edu Ma F.Y.; frank.ma@monash.edu Badal S.S.; shawn.badal@gilead.com Liles J.T.; john.liles@gilead.com | en |
dc.description.grant | No: 1058175 Organization: (NHMRC) *National Health and Medical Research Council* Organization No: 501100000925 Country: Australia | en |
dc.identifier.affiliationext | (Leong, Ozols, Kanellis, Nikolic-Paterson, Ma) Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia | - |
dc.identifier.affiliationext | (Badal, Liles) Gilead Sciences, Foster City, CA 94404, United States | - |
dc.identifier.affiliationmh | (Leong, Ozols, Kanellis, Nikolic-Paterson, Ma) Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.openairetype | Article | - |
crisitem.author.dept | Nephrology | - |
Appears in Collections: | Articles |
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