Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism

Mehrotra, Purvi; Patel, Janaki M.; Ivancic, Carlie M.; Collett, Jason A.; Basile, David P.

doi:10.1038/ki.2015.200

Cited by 86 publications

(113 citation statements)

References 56 publications

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“…Besides, it has been suggested that Sulodexide can maintain or restore endothelial cells function [44,45], whether Sulodexide has beneficial effects on endothelial cells in CIN and other molecular mechanisms remain to be determined in the future. As a common AKI, CIN not only can result in longer in-hospital stay and higher rates of in-hospital complications and 1-year mortality, but also can lead to AKI-chronic kidney disease transition, another big clinical problem [46,47]. In a word, CIN is still a big challenge in the clinical practice [48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H₂O₂-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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“…5B). Fibrosis progression is known to involve Th17 activation (35) and accumulation of M2-polarized macrophages (36), whereas regulatory T cells could be protective (37). However, no noticeable differences were found in these populations after subset analysis, suggesting that neither T cell (Fig.…”

Section: Early MC Activation Promotes Long-term Organ Atrophy and Fibmentioning

confidence: 97%

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Danelli

Madjène

Madera-Salcedo

et al. 2017

The Journal of Immunology

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Ischemia–reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell–depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.

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“…The maintenance of these imbalances seems to favor the inflammatory microenvironment, which would explain their prognostic implications, and therapeutics potentials, from NAFLD, to cirrhosis, and HCC (28, 51). In addition, the role of the IL-17 axis in fibrogenesis has been shown in organs other than the liver, including the heart (119, 120), lung (121), and kidney (122). This model has been reasonably proven by evidence of elevation of neutrophils, Th17, and related cytokines, both in the systemic circulation and in the liver (28, 29, 70).…”

Section: Underlying Mechanisms Pathways and Relationship Between Cementioning

confidence: 99%

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Paquissi

2016

Front. Immunol.

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Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.

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Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism

Cited by 86 publications

References 56 publications

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia–Reperfusion Injury

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

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