Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury

Background: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. Methods: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Results: Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. Conclusion: S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target

Hierarchical clustering of differentially expressed miRNAs and mRNAs in endometrioid endometrial carcinoma (S1_T, S2_T, S3_T) and adjacent non-tumorous tissues (S1_N, S2_N, S3_N).

<p>Hierarchical clustering of differentially expressed miRNAs and mRNAs in endometrioid endometrial carcinoma (S1_T, S2_T, S3_T) and adjacent non-tumorous tissues (S1_N, S2_N, S3_N).</p

MiRNA-gene network of the cell cycle pathway in endometrioid endometrial carcinoma.

<p>Protein symbols were marked according to gene expression pattern. Those with red frames are up regulated while those with blue frames are down regulated in endometrioid endometrial carcinoma tissues. Similarly, miRNAs with blue background were down regulated while the miRNA with red ground were up regulated in endometrioid endometrial carcinoma tissues.</p

QPCR expression on QPCR-validated genes and miRNAs in the cell cycle pathway.

<p>*: <i>p</i><0.05; **: <i>p</i><0.01.</p

Pathway analysis based on miRNA-targeted differentially expressed genes.

<p>Pathway analysis based on miRNA-targeted differentially expressed genes.</p

Summary of miRNA sequencing.

<p>Summary of miRNA sequencing.</p

Summary of mRNA sequencing.

<p>Summary of mRNA sequencing.</p

Sequence variants identified from transcriptome data.

<p>Sequence variants identified from transcriptome data.</p