Dataset Information

IKK? is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells.

ABSTRACT: The recovery phase after kidney ischemia/reperfusion (IR) injury is often associated with the suppression of inflammation and the proliferation of tubular epithelial cells (TECs). The duration of this phase is often determined by the suppression of inflammation and the proliferation of TECs. Several lines of evidence suggest that I?B kinase ? (IKK?) not only promotes the production of anti-inflammatory factors and/or prevents the production of inflammatory factors, but also induces the accompanying cell differentiation and regeneration, and suppresses inflammation. We therefore hypothesized that IKK? could participate in the kidney repair after IR injury and have used a mouse model of acute kidney injury (AKI) to test this. We found that IKK? mediated the repair of the kidney via infiltrated regulatory T (Treg) cells, which can produce anti-inflammatory cytokine IL10, and that IKK? also increased the proliferation of the surviving TECs and suppressed of inflammation. In addition, the expression of indoleamine 2,3-dioxygenase (IDO) in TECs is consistent with the infiltration of IL10-producing Treg cells. We conclude that IKK? is involved in kidney recovery and regeneration through the Treg cells that can produce IL10, which might be a potential therapeutic target that can be used to promote kidney repair after IR injury.

SUBMITTER: Wan X

PROVIDER: S-EPMC4486855 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells.

Wan Xin X Hou Li-Jun LJ Zhang Li-Yuan LY Huang Wen-Juan WJ Liu Lin L Zhang Qian Q Hu Bo B Chen Wen W Chen Xin X Cao Chang-Chun CC

Disease models & mechanisms 20150514 7

The recovery phase after kidney ischemia/reperfusion (IR) injury is often associated with the suppression of inflammation and the proliferation of tubular epithelial cells (TECs). The duration of this phase is often determined by the suppression of inflammation and the proliferation of TECs. Several lines of evidence suggest that IκB kinase α (IKKα) not only promotes the production of anti-inflammatory factors and/or prevents the production of inflammatory factors, but also induces the accompany ...[more]

PMID: 26035380

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Project description:BackgroundRetinal function is ordered by interactions between transcriptional and posttranscriptional regulators at the molecular level. These regulators include transcription factors (TFs) and posttranscriptional factors such as microRNAs (miRs). Some studies propose that miRs predominantly target the TFs rather than other types of protein coding genes and such studies suggest a possible interconnection of these two regulators in co-regulatory networks.ResultsOur lab has generated mRNA and miRNA microarray expression data to investigate time-dependent changes in gene expression, following induction of ischemia-reperfusion (IR) injury in the rat retina. Data from different reperfusion time points following retinal IR-injury were analyzed. Paired expression data for miRNA-target gene (TG), TF-TG, miRNA-TF were used to identify regulatory loop motifs whose expressions were altered by the IR injury paradigm. These loops were subsequently integrated into larger regulatory networks and biological functions were assayed. Systematic analyses of the networks have provided new insights into retinal gene regulation in the early and late periods of IR. We found both overlapping and unique patterns of molecular expression at the two time points. These patterns can be defined by their characteristic molecular motifs as well as their associated biological processes. We highlighted the regulatory elements of miRs and TFs associated with biological processes in the early and late phases of ischemia-reperfusion injury.ConclusionsThe etiology of retinal ischemia-reperfusion injury is orchestrated by complex and still not well understood gene networks. This work represents the first large network analysis to integrate miRNA and mRNA expression profiles in context of retinal ischemia. It is likely that an appreciation of such regulatory networks will have prognostic potential. In addition, the computational framework described in this study can be used to construct miRNA-TF interactive systems networks for various diseases/disorders of the retina and other tissues.

Dataset Information

IKK? is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells.

Publications

IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells.

Similar Datasets

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