RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES−/−) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

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Rheumatoid arthritis (RA) is associated with atherosclerosis. However, the relationship between RA and peripheral arterial occlusive disease (PAOD) remains unclear. We used a national health insurance database to identify a cohort of 30,812 patients diagnosed with RA between 2000 and 2011. Each RA patient was frequency-matched according to age and sex with a patient without RA from a control cohort. A multivariate Cox proportional hazards model was used to analyse the adjusted risk of PAOD. The incidence of PAOD was 1.73-fold higher (95% confidence interval [CI] = 1.57-1.91) in the RA cohort than in the non-RA cohort. The adjusted risk of PAOD was the highest in the patients with RA aged ≤ 49 years (hazard ratio [HR] = 3.39, 95% CI = 2.66-4.32). Patients with RA and various comorbidities showed a significantly higher risk of PAOD (HR = 9.62, 95% CI = 4.86-19.1) compared with control patients without comorbidity. The risk of PAOD increased during the first year of follow-up. In conclusion, patients with RA have an independently higher risk of PAOD compared with the general population. Patients with RA and various comorbidities and those at a young age and early stage of the disease have an increased risk of PAOD.

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Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan’s universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan–Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer’s disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47–5.31) versus 2.08 (95% CI: 1.83–2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia.

Autophagy, a prosurvival mechanism offers a protective role during acute kidney injury.We show novel findings on the functional role of RNA binding protein, HuR during hypoxia-induced autophagy in renal proximal tubular cells-2 (HK-2). HK-2 cells showed upregulated expressions of HuR and autophagy-related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin-RNA-mediated loss of HuR function in HK-2 cells significantly decreased ATG7 and ATG16L1 protein expressions. Bioinformatics prediction revealed HuR motif binding on the coding region of ATG7 and AU-rich element at 3′UTR ATG16L1 messnger RNA (mRNA). The RNA immunoprecipitation study showed that HuR was predominantly associated with ATG7 and ATG16L1 mRNAs under hypoxia. In addition, HuR enhanced autophagosome formation by regulating LC3II expressions. These results show that HuR regulates ATG7 and ATG16L1 expressions and thereby mediate autophagy in HK-2 cells. Importantly, HuR knockdown cells underwent apoptosis during hypoxia as observed through the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Collectively, these findings show the crucial role of HuR under hypoxia by regulating autophagy and suppressing apoptosis in renal tubular cells. Abbreviations: HuR, human antigen R; ATG7, autophagy related 7; ATG16L1, autophagy related 16 like 1; DAPI, 4′, 6-diamidino-2-phenylindole; ANOVA, analysis of variance; CDS, coding sequence; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. *Kalaiselvi Palanisamy, Tsung-Hsun Tsai and Tung-Min Yu contributed equally to this study.