RGD Reference Report - Depletion of macrophages slows the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Depletion of macrophages slows the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats.

Authors: Poudel, Bibek  Shields, Corbin A  Brown, Andrea K  Ekperikpe, Ubong  Johnson, Tyler  Cornelius, Denise C  Williams, Jan M 
Citation: Poudel B, etal., Am J Physiol Renal Physiol. 2020 Jun 1;318(6):F1489-F1499. doi: 10.1152/ajprenal.00100.2020. Epub 2020 May 11.
RGD ID: 34888223
Pubmed: (View Article at PubMed) PMID:32390513
DOI: Full-text: DOI:10.1152/ajprenal.00100.2020

Recently, we reported that obese Dahl salt-sensitive (SS) leptin receptor mutant (SSLepRmutant) rats display progressive renal injury. The present study demonstrated that the early development of renal injury in the SSLepRmutant strain is associated with an increase in the renal infiltration of macrophages compared with lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SSLepRmutant strain. Four-week-old SS and SSLepRmutant rats were treated with either vehicle (PBS) or clodronate (50 mg/kg ip, 2 times/wk) for 4 wk. While the administration of clodronate did not reduce renal macrophage infiltration in SS rats, clodronate decreased macrophages in the kidneys of SSLepRmutant rats by >50%. Interestingly, clodronate significantly reduced plasma glucose, insulin, and triglyceride levels and markedly improved glucose tolerance in SSLepRmutant rats. Treatment with clodronate had no effect on the progression of proteinuria or renal histopathology in SS rats. In the SSLepRmutant strain, proteinuria was markedly reduced during the first 2 wk of treatment (159 ± 32 vs. 303 ± 52 mg/day, respectively). However, after 4 wk of treatment, the effect of clodronate was no longer observed in the SSLepRmutant strain (346 ± 195 vs. 399 ± 50 mg/day, respectively). The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal fibrosis versus SS rats. Treatment with clodronate significantly decreased glomerular injury and renal fibrosis in the SSLepRmutant strain. Overall, these data indicate that the depletion of macrophages improves metabolic disease and slows the early progression of renal injury in SSLepRmutant rats.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)
Leprem2Mcwi  (leptin receptor; zinc finger nuclease induced mutant 2, Medical College of Wisconsin)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)

Strains
SS-Leprem2Mcwi  (NA)


Additional Information