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

Jin, Yuanmeng; Liu, Ruijie; Xie, Jingyuan; Xiong, Huabao; He, John Cijiang; Chen, Nan

doi:10.1038/labinvest.2013.64

Cited by 89 publications

(69 citation statements)

References 41 publications

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“…These findings are consistent with earlier reports that endogenous IL-10 deficiency was involved in both sclerosis and fibrosis of renal tissue induced by many factors such as ureteral obstruction 34 and ischemia-reperfusion injury. 35 A reduction in IL-10 level was observed during AngII administration 6 and AngII–induced vascular effects were prevented by exogenously applied IL-10.…”

Section: Discussionsupporting

confidence: 93%

Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level

et al. 2017

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Interleukin-10 (IL-10) has been suggested to play a protective role in angiotensin II (AngII) induced cardiovascular disorders. This study examined the role of endogenous IL-10 in salt-sensitive hypertension (SSH) and renal injury induced by AngII. Responses to chronic AngII (400 ng/min/kg bw; osmotic minipump) infusion were evaluated in IL-10 gene knockout (IL-10KO) mice, fed with either normal (NS; 0.3% NaCl) or high (HS; 4% NaCl) salt diets and these responses were compared to those in wild type (WT) mice. NS or HS diets were given alone for the first 2 weeks and then with AngII treatment for additional 2 weeks (n=6 in each group). Arterial pressure was continuously monitored by implanted radio-telemetry and 24 hour (hr) urine collection was performed by metabolic cages on the last day of the experimental period. Basal mean arterial pressure (MAP) was lower in IL-10KO than in WT (98±3 vs 113±3, mmHg) mice. MAP responses to NS/HS alone or to the AngII+NS treatment were similar in both strains. However, the increase in MAP induced by the AngII+HS treatment was significantly lower in IL-10KO (15±5% vs 37±3%) compared to WT. Renal tissue eNOS expression (~3 folds) as well as urinary excretion of nitric oxide (NO) metabolites, nitrate/nitrite (1.2±0.1 vs 0.2±0.02, μM/24 hr) were higher in IL-10KO compared to WT. These results indicate that an increase in NO production helps to mitigate SSH induced by AngII and suggest that a compensatory interaction between IL-10 and NO exists in modulating AngII induced responses during HS intake.

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Section: Discussionsupporting

confidence: 93%

Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level

et al. 2017

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“…Klotho protects against renal damage, and expression of this gene is reduced following ageing and acute kidney injury (Figure S3A) (Kurosu et al, 2005; Panesso et al, 2014). IL-10 is an anti-inflammatory cytokine that ameliorates renal injury following cisplatin treatment (Jin et al, 2013; Ling et al, 2011). We asked whether the CRISPR/Cas9 TGA system could be used to induce the expression of Klotho or IL-10 in vivo to treat acute kidney injury.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

Liao

Hatanaka

Araoka

et al. 2017

Cell

366

264

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SUMMARY Current genome-editing systems generally rely on the creation of DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. The CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat several mouse models of human diseases. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to observable phenotypic changes, and amelioration of disease symptoms. This establishes new avenues for developing targeted epigenetic therapies against human diseases.

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“…This protective effect of IL-10 is demonstrated in the context of renal inflammation in the unilateral ureteral obstruction model. More severe inflammation develops in the kidney of mice lacking IL-10 compared with wild-type controls (44). Overall, the dominant effect of MPO-ANCA on monocytes is a reduction in IL-10 secretion, which would be expected to promote inflammation and disease in patients.…”

Section: Discussionmentioning

confidence: 97%

Anti-myeloperoxidase antibodies attenuate the monocyte response to LPS and shape macrophage development

Popat¹,

Hakki²,

Thakker³

et al. 2017

JCI Insight

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

Cited by 89 publications

References 41 publications

Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level

Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

Anti-myeloperoxidase antibodies attenuate the monocyte response to LPS and shape macrophage development

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