Document Detail

Inducible expression of kallikrein in renal tubular cells protects mice against spontaneous lupus nephritis.
MedLine Citation:
PMID:  23280471     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To ascertain whether engineered expression of kallikreins within the kidneys, using an inducible Cre/loxP system, can ameliorate murine lupus nephritis.
METHODS: In mice with a lupus-prone genetic background, we engineered the expression of tamoxifen-inducible Cre recombinase under the control of a kidney-specific promoter whose activation initiates murine kallikrein-1 expression within the kidneys. These transgenic mice were injected with either tamoxifen or vehicle at age 2 months and then were monitored for 8 months for kallikrein expression and disease.
RESULTS: Elevated expression of kallikrein was detected in the kidney and urine of tamoxifen-injected mice but not in controls. At age 10 months, all vehicle-injected mice developed severe lupus nephritis, as evidenced by increased proteinuria (mean ± SD 13.43 ± 5.65 mg/24 hours), increased blood urea nitrogen (BUN) and serum creatinine levels (39.86 ± 13.45 mg/dl and 15.23 ± 6.89 mg/dl, respectively), and severe renal pathology. In contrast, the tamoxifen-injected mice showed significantly reduced proteinuria (6.6 ± 4.12 mg/24 hours), decreased BUN and serum creatinine levels (15.71 ± 8.17 mg/dl and 6.64 ± 3.39 mg/dl, respectively), and milder renal pathology. Tamoxifen-induced up-regulation of renal kallikrein expression increased nitric oxide production and dampened renal superoxide production and inflammatory cell infiltration, alluding to some of the pathways through which kallikreins may be operating within the kidneys.
CONCLUSION: Local expression of kallikreins within the kidney has the capacity to dampen lupus nephritis, possibly by modulating inflammation and oxidative stress.
Xinli Shao; Ru Yang; Mei Yan; Yajuan Li; Yong Du; Indu Raman; Bo Zhang; Edward K Wakeland; Ward Wakeland; Peter Igarashi; Chandra Mohan; Quan-Zhen Li
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-24     Revised Date:  2013-05-14    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  780-91     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
University of Texas-Southwestern Medical Center, Dallas, TX 75235, USA.
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MeSH Terms
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Green Fluorescent Proteins / genetics
Integrases / genetics
Kidney Tubules / cytology,  physiology*
Lac Operon / genetics
Lupus Nephritis / genetics*,  metabolism,  physiopathology
Mice, Congenic
Mice, Inbred Strains
Mice, Transgenic
Nitric Oxide / metabolism
Oxidative Stress / physiology*
Selective Estrogen Receptor Modulators / toxicity
Superoxides / metabolism
Tamoxifen / toxicity
Tissue Kallikreins / genetics*,  metabolism
Grant Support
P30-DK-079328-03/DK/NIDDK NIH HHS; R01-AR-050812/AR/NIAMS NIH HHS; R03-AR-055778/AR/NIAMS NIH HHS
Reg. No./Substance:
0/Selective Estrogen Receptor Modulators; 0/enhanced green fluorescent protein; 10102-43-9/Nitric Oxide; 10540-29-1/Tamoxifen; 11062-77-4/Superoxides; 147336-22-9/Green Fluorescent Proteins; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases; EC Kallikreins
Erratum In:
Arthritis Rheum. 2013 Apr;65(4):1106
Note: Wakeland, Ward [corrected to Wakeland, Edward K]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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