期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 179, 期 3, 页码 1120-1128出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2011.05.011
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资金
- Foundation for Health and Rehabilitation through the Norwegian Rheumatology Organization [2004/2/0250]
- Northern Norway Regional Health Authority [SFP-100-04, SFP-101-04]
- University of Tromso
An acquired loss of renal DNaseI promotes transformation of mild mesangial lupus nephritis into membranoproliferative 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 whether silencing of the renal DNaseI gene is an organ-specific feature or whether loss of DNaseI reflects a systemic error in mice with sever lupus nephritis. The present results demonstrate normal or elevated levels of DNaseI mRNA and enzyme activity in liver, spleen, and serum samples from (NZBxNZW)F1 mice throughout all the 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, whereas six other nucleases (DNaseII1 to 3, caspase-activated DNase, Dnase2a, and endonuclease G) were approximately normally expressed in kidneys, liver, and spleen. Loss of renal DNaseI was not accompanied by changes in serum DNaseI activity, suggesting independent mechanisms of DNaseI regulation in circulation and in kidneys and an absence of compensatory up-regulation of serum DNaseI activity in the case of renal DNaseI deficiency. Thus, silencing of renal DNaseI is a unique renal feature in membranoproliferative lupus nephritis. Determining the mechanism(s) responsible for DNaseI down-regulation might lead to the generation of new therapeutic targets to treat and prevent progressive lupus nephritis. (Am J Pathol 2011, 179:1120-1128; DOI: 10.1016/j.ajpath.2011.05.011)
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