RGD Reference Report - Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice.

Authors: Lim, AK  Ma, FY  Nikolic-Paterson, DJ  Thomas, MC  Hurst, LA  Tesch, GH 
Citation: Lim AK, etal., Diabetologia. 2009 May 23.
RGD ID: 2311340
Pubmed: PMID:19466391   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-009-1399-3   (Journal Full-text)

AIMS/HYPOTHESIS: Macrophage-mediated renal injury plays an important role in the development of diabetic nephropathy. Colony-stimulating factor (CSF)-1 is a cytokine that is produced in diabetic kidneys and promotes macrophage accumulation, activation and survival. CSF-1 acts exclusively through the c-fms receptor, which is only expressed on cells of the monocyte-macrophage lineage. Therefore, we used c-fms blockade as a strategy to selectively target macrophage-mediated injury during the progression of diabetic nephropathy. METHODS: Obese, type 2 diabetic db/db BL/KS mice with established albuminuria were treated with a neutralising anti-c-fms monoclonal antibody (AFS98) or isotype matched control IgG from 12 to 18 weeks of age and examined for renal injury. RESULTS: Treatment with AFS98 did not affect obesity, hyperglycaemia, circulating monocyte levels or established albuminuria in db/db mice. However, AFS98 did prevent glomerular hyperfiltration and suppressed variables of inflammation in the diabetic kidney, including kidney macrophages (accumulation, activation and proliferation), chemokine CC motif ligand 2 levels (mRNA and urine protein), kidney activation of proinflammatory pathways (c-Jun amino-terminal kinase and activating transcription factor 2) and Tnf-alpha (also known as Tnf) mRNA levels. In addition, AFS98 decreased the tissue damage caused by macrophages including tubular injury (apoptosis and hypertrophy), interstitial damage (cell proliferation and myofibroblast accrual) and renal fibrosis (Tgf-beta1 [also known as Tgfb1] and Col4a1 mRNA). CONCLUSIONS/INTERPRETATION: Blockade of c-fms can suppress the progression of established diabetic nephropathy in db/db mice by targeting macrophage-mediated injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOCol4a1 (Mus musculus)2311340; 2311340associated with Diabetes Mellitus more ...RGD 
Diabetic Nephropathies disease_progressionISOCsf1r (Mus musculus)2311340; 2311340associated with Diabetes Mellitus and Type 2RGD 
Diabetic Nephropathies  IEP 2311340associated with Diabetes Mellitus more ...RGD 
Diabetic Nephropathies disease_progressionIMP 2311340associated with Diabetes Mellitus and Type 2RGD 

Objects Annotated

Genes (Rattus norvegicus)
Col4a1  (collagen type IV alpha 1 chain)
Csf1r  (colony stimulating factor 1 receptor)

Genes (Mus musculus)
Col4a1  (collagen, type IV, alpha 1)
Csf1r  (colony stimulating factor 1 receptor)

Genes (Homo sapiens)
COL4A1  (collagen type IV alpha 1 chain)
CSF1R  (colony stimulating factor 1 receptor)


Additional Information