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dc.contributor.authorSeredkina, Natalya
dc.contributor.authorRekvik, Ole Petter
dc.date.accessioned2011-08-25T12:01:43Z
dc.date.available2011-08-25T12:01:43Z
dc.date.issued2011
dc.description.abstractAn acquired loss of renal DNaseI has recently been shown to promote transformation of mild mesangial lupus nephritis into membrano-proliferative end-stage organ disease. In this study, we analyzed expression profiles of DNaseI in other organs of lupus-prone (NZBxNZW)F1 mice during disease progression to determine if silencing of the renal DNaseI gene is an organ specific feature or if loss of DNaseI reflects a systemic error in mice with sever lupus nephritis. Our results demonstrate normal or elevated levels of DNaseI mRNA and enzyme activity in liver, spleen and serum samples of (NZBxNZW)F1 mice throughout all stages of lupus nephritis. DNaseI activity was dramatically reduced only in kidneys of mice with sever nephritis and was the only nuclease that was down-regulated, while 6 other nucleases (DNaseIl1-3, caspase activated deoxyribonuclease, Dnase2a, and endonuclease G) were largely normally expressed in kidneys, liver and spleen. Loss of renal DNaseI was not accompanied by changes in serum DNaseI activity, suggesting an independent mechanism of DNaseI regulation in circulation and in kidneys, and an absence of compensatory upregulation of serum DNaseI activity in case of renal DNaseI deficiency. Thus, silencing of renal DNaseI is a unique renal feature in membrano-proliferative lupus nephritis. Determination of mechanism(s) responsible for DNaseI down-regulation is a future step in generation of new therapeutic targets to treat and prevent progressive lupus nephritis.en
dc.descriptionAccepted manuscript version, reprinted with permission (Elsevier). <br/> Published version available at <a href=http://dx.doi.org/10.1016/j.ajpath.2011.05.011>http://dx.doi.org/10.1016/j.ajpath.2011.05.011</a> <br/>This article is part of Natalya Serdkina's doctoral thesis which is available in Munin at <a href=http://hdl.handle.net/10037/3563>http://hdl.handle.net/10037/3563</a>en
dc.identifier.citationAmerican Journal of Pathology (2011) Vol. 179, Issue 3, p 1120-1128en
dc.identifier.doidoi: 10.1016/j.ajpath.2011.05.011
dc.identifier.urihttps://hdl.handle.net/10037/3564
dc.identifier.urnURN:NBN:no-uit_munin_3284
dc.language.isoengen
dc.publisherElsevieren
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Other health science disciplines: 829en
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Andre helsefag: 829en
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Nephrology, urology: 772en
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Nefrologi, urologi: 772en
dc.titleAcquired loss of renal nuclease activity is restricted to DNase I and is an organselective feature in murine lupus nephritisen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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