RGD Reference Report - New immunosuppresor strategies in the treatment of murine lupus nephritis. - Rat Genome Database

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New immunosuppresor strategies in the treatment of murine lupus nephritis.

Authors: Alperovich, G  Rama, I  Lloberas, N  Franquesa, M  Poveda, R  Goma, M  Herrero-Fresneda, I  Cruzado, JM  Bolanos, N  Carrera, M  Grinyo, JM  Torras, J 
Citation: Alperovich G, etal., Lupus. 2007;16(1):18-24.
RGD ID: 7245502
Pubmed: PMID:17283580   (View Abstract at PubMed)

Renal involvement in systemic lupus erythematosus is a common complication that significantly worsens morbidity and mortality. Although treatment with corticosteroids and cytotoxic drugs may be useful in many cases, morbidity associated with these drugs and the relapsing nature of the disease make it necessary to develop new treatment strategies. Five-month old female NZB/W F1 mice were divided into the following groups: CYP group (n = 10), cyclophosphamide (CYP) 50 mg/kg intraperitoneally every 10 days; RAPA 1 group (n = 10) oral daily sirolimus (SRL), 1 mg/kg; RAPA 12 group (n = 13), oral daily SRL, 12mg/kg; FTY group (n = 10), oral fingolimod (FTY720), 2 mg/kg three times per week. An additional group of 13 non-treated mice were used as a control (control group). Follow-up was performed over four months. Animal survival, body weight, anti-DNA antibodies and proteinuria were determined. Kidneys were processed for conventional histology and immunofluorescence for IgG and complement. Total histological score (HS) was the sum of mesangial expansion, endocapillary proliferation glomerular deposits, extracapillary proliferation, interstitial infiltrates, tubular atrophy and interstitial fibrosis. All treated groups had lower proteinuria at the end of the follow-up with respect to the control group (P < 0.0001). Serum anti-DNA antibodies were appropriately controlled in RAPA 1 and CYP groups, but not in FTY or RAPA 12 groups. SRL and CYP arrested, and perhaps reversed almost all histological lesions. FTY720 ameliorated histological lesions but did not control mesangial expansion or interstitial infiltrates. SRL produces great improvement in murine lupus nephritis, while FTY720 seems a promising alternative if used in appropriate doses.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lupus nephritis  ISOMtor (Mus musculus)7245502; 7245502 RGD 
lupus nephritis  IMP 7245502 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information