RGD Reference Report - Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model. - Rat Genome Database

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Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model.

Authors: Jin, Y  Liu, R  Xie, J  Xiong, H  He, JC  Chen, N 
Citation: Jin Y, etal., Lab Invest. 2013 Jul;93(7):801-11. doi: 10.1038/labinvest.2013.64. Epub 2013 Apr 29.
RGD ID: 7257564
Pubmed: PMID:23628901   (View Abstract at PubMed)
DOI: DOI:10.1038/labinvest.2013.64   (Journal Full-text)

Interleukin-10 functions as a general immunosuppressive cytokine, which also negatively regulates inflammatory responses through complex mechanisms. Recent studies suggested that IL-10 may also inhibit fibrosis in various diseased models. However, the role of IL-10 in renal fibrosis has not been demonstrated. Here, we investigated the effects of IL-10 in the development of renal tubulointerstitial fibrosis by creating the unilateral ureteral obstruction (UUO) model in IL-10 knockout (-/-) mice. We performed sham or unilateral ureteral obstruction surgery in 8-week-old IL-10-/- male mice and age and sex-matched wild type littermates. Mice were killed at 7 days or 14 days post surgery and renal tissues were obtained for RNA, protein, and immunohistochemical analysis. Our results found IL-10 deficiency resulted in enhanced renal fibrosis demonstrated by more severe tubular injury and collagen deposition and higher expression of pro-fibrotic genes (including alpha-SMA, MMP-2, fibronectin, FSP-1 and vimentin). Our results also found IL-10-/- UUO mice developed more severe renal inflammation with a significant increase in inflammatory cells infiltration, and upregulation of inflammatory chemokines (MCP-1 and RANTES), and cytokines (TNF-alpha, IL-6, IL-8, and M-CSF). Further study revealed that enhanced renal inflammation and fibrosis was associated with significantly increased activation of both TGF-beta/Smad3 and NF-kappaB signaling pathways. In summary, our study provides the direct evidence that IL-10 is an endogenous cytokine that has a key role in protecting against development of renal inflammation and fibrosis. Enhancement of IL-10 expression could be a potential anti-fibrosis therapy for patients with chronic kidney diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ureteral obstruction  ISOCsf1 (Mus musculus)7257564; 7257564mRNA:increased expression:kidneyRGD 
ureteral obstruction  IEP 7257564mRNA:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf1  (colony stimulating factor 1)

Genes (Mus musculus)
Csf1  (colony stimulating factor 1 (macrophage))

Genes (Homo sapiens)
CSF1  (colony stimulating factor 1)

Additional Information