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Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) resulting in an abrupt deterioration of kidney function. CXC chemokine ligand 16 (CXCL16) contributes significantly to the pathogenesis of renal injury. However, the signaling pathway mechanisms of CXCL16 in IRI-induced AKI remains obscured. In this study, we examined the role of the CXCL16/ Rho Associated Coiled-Coil Containing Protein Kinase-1 (ROCK1) signaling pathway in AKI induced by IRI. In vivo, CXCL16 was induced markedly after IRI. Mice treated with anti-CXCL16 antibody displayed less severe renal dysfunction and tubular injury in response to IRI compared with vehicle-treated mice. Inhibition of CXCL16 substantially reduced apoptotic cells and suppresses caspase-3 activation in the kidneys of mice following IRI. Additionally, CXCL16 inhibition profoundly decreased the production of TNF-α, IL-1β and IL-6 in the kidneys of mice post IRI. Furthermore, the level of ROCK1 protein was upregulated in the kidney in response to IRI, an effect that was abolished by CXCL16 inhibitor. Finally, treatment with Y-27632 (a ROCK1 inhibitor) attenuated deterioration of renal function and tubular damage of mice after IRI. Administration of Y-27632 ameliorated apoptosis in the IRI-treated kidneys of mice. In injured HK-2 cells, CXCL16 activated ROCK1 resulting in the upregulation of caspase-3 protein and pro-inflammatory molecules, which was abolished by Y-27632. In summary, our findings demonstrate that CXCL16/ROCK1 signaling pathway may play an important role in the pathogenesis of IRI-induced AKI.

The pathological physiology of end-stage renal disease is characterized by renal fibrosis, for which suitable therapeutics have not yet been developed. Early tubular damage in ischemia-reperfusion (IR) injury induced acute kidney injury (AKI) is highly relevant to later fibrosis, but the mechanism remains unclear. Moreover, more and more evidence has proven that long non-coding ribonucleic acids (lncRNA) regulate gene expression associated with renal fibrosis. Therefore, we analyzed lncRNA profiles in the kidneys of mice using RNA sequencing during the pathogenesis of IR-induced renal fibrosis. Our results showed that expression levels of 43 lncRNAs and 141 lncRNAs were respectively significantly changed 7 days and 2 weeks after IR treatment. We predicted the functions of the differentially expressed (DE) lncRNAs and target genes with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Interaction networks of lncRNAs, microRNAs (miRNAs) and mRNA were constructed based on the correlation analysis of the DE genes. Based on these informations, we further verified lncRNA (Gm12840) play competing endogenous RNA (ceRNA) mechanism with miR-677-5p to meidiate TGF-β1 induced fibroblast activation via Wnt-induced secreted protein-1 (WISP1)/ protein kinase B (Akt) signaling pathway. Our findings identify that lncRNAs are involved in IR-induced late fibrosis of kidney and may represent a systematic perspective on the important function of IR-induced renal fibrosis as well as new therapeutic targets. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (81860130), Natural Science Foundation of Guangdong province (2016A030313376), Guangdong Province Science and Technology Planning Project (2017B020247035, 2014A020212612). Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: All experiments using animals were approved by the Institutional Animal Care and Use Committee of the First People hospital of Foshan and breed as approved by the Institutional Animal Care protocol.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main enzymes that produce oxidative stress, which plays an important role in painful diabetic neuropathy. Curcumin has been reported to exert an antinociceptive effect in a rat model of diabetic neuropathy by suppressing oxidative stress in the spinal cord. However, it remains unknown whether the mechanism by which curcumin ameliorates diabetic neuropathy can be attributed to spinal NADPH oxidases. This study was designed to determine the effect of curcumin on diabetic neuropathy and to investigate its precise mechanism in relation to NADPH oxidase-mediating oxidative stress in the spinal cord. Diabetic neuropathy was induced in Sprague-Dawley rats by intraperitoneal injection with 1% streptozotocin (STZ; 60 mg/kg). After the onset of diabetic neuropathy, a subset of the diabetic rats received daily intragastric administrations of curcumin (200mg/kg) or intraperitoneal injections of apocynin (2.5mg/kg) for 14 consecutive days, whereas other diabetic rats received equivalent volumes of normal saline (NS). STZ resulted in diabetic neuropathy with hyperglycemia and a lower paw withdrawal threshold (PWT), accompanied by elevations in the expression of the NADPH oxidase subunits p47(phox) and gp91(phox) and in the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and a reduction in superoxide dismutase (SOD) activity (P