Renal fibrosis is associated with the reduction in the functional renal parenchyma and in most cases progresses to end-stage kidney failure, a devastating condition that requires lifelong dialysis or kidney transplantation. However, due to the extreme complexity in the pathogenesis of renal fibrosis and our limited knowledge, therapeutic options for renal fibrosis in the clinical setting are still scarce and often ineffective. Hence, further studies on the molecular mechanisms underlying renal fibrosis are compellingly needed. Multiple miRNAs have demonstrated to participate in kidney diseases in a TGF-β dependent or independent manner, but there is very little known about miR-155-5p on renal fibrosis. In the present study, we firstly explored the expression level and functions of miR-155-5p in the setting of renal fibrosis. Our research revealed that miR-155-5p is highly expressed in kidney tissues from patients and unilateral ureteral obstruction (UUO) rat models, and miR-155-5p knockdown significantly blocks renal fibrosis both in vivo and in vitro. In mechanism, our data demonstrate that miR-155-5p promotes renal fibrosis by increasing the phosphorylated activation of STAT3 via targeting SOCS1/6. Altogether, our findings highlight a miR-155-5p/SOCS/STAT3 axis in the pathogenesis of renal fibrosis, which may provide promising therapeutic targets for clinical prevention of this disease.
Aims. Many previous studies have examined the effect of different hydration strategies on prevention of contrast-induced acute kidney injury (CI-AKI), but the optimal strategy is unknown. We performed a network meta-analysis (NWM) of these previous studies to identify the optimal strategy. Methods and Results. Web of Science, PubMed, OVID Medline, and Cochrane Library were searched from their inception dates to September 30, 2018. Randomized controlled trials (RCTs) were selected based on strict inclusion criteria, and a Bayesian NWM was performed using WinBUGS V.1.4.3. We finally analyzed 60 eligible RCTs, which examined 21,293 patients and 2232 CI-AKI events. Compared to intravenous 0.9% sodium chloride (reference), intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard guided hydration (0.32 [0.14, 0.70]) significantly reduced the occurrence of CI-AKI. Oral hydration and intravenous 0.9% sodium chloride were each noninferior to no hydration in preventing CI-AKI. Intravenous 0.9% sodium chloride, sodium bicarbonate, and hemodynamic guided hydration were each noninferior to oral hydration in preventing CI-AKI. Based on surface under the cumulative ranking curve values, the RenalGuard system was best (0.974) and hemodynamic guided hydration was second best (0.849). Conclusion. There was substantial evidence to support the use of RenalGuard or hemodynamic guided hydration for preventing CI-AKI in high-risk patients, especially those with chronic kidney disease or cardiac dysfunction.
Purpose: Contrast-induced acute kidney injury (CI-AKI) resulting from administration of iodinated contrast media (CM) is the third leading cause of hospital-acquired acute kidney injury and is associated with substantial morbidity and mortality. Deteriorated renal microcirculation plays an important role in CI-AKI. Limb ischemic preconditioning (LIPC), where brief and non-injurious ischemia/reperfusion is applied to a limb prior to the administration of the contrast agent, is emerging as a promising strategy for CI-AKI prevention. However, it is not known whether the renal protection of LIPC against CI-AKI is mediated by regulation of renal microcirculation and the molecular mechanisms remain largely unknown. Methods: In this study, we examined the renal cortical and medullary blood flow in a stable CI-AKI model using 5/6-nephrectomized (NE) rat. The LIPC and sham procedures were performed prior to the injection of CM. Furthermore, we analyzed renal medulla hypoxia using in vivo labeling of hypoxyprobe. Pharmacological inhibitions and western blotting were used to determine the underlying molecular mechanisms. Results: In this study, we found LIPC significantly ameliorated CM-induced reduction of medullary blood flow and attenuated CM-induced hypoxia. PI3K inhibitor (wortmannin) treatment blocked the regulation of medullary blood flow and the attenuation of hypoxia of LIPC. Phosphorylation of Akt/eNOS was significantly decreased via wortmannin treatment compared with LIPC. Nitric oxide synthase-inhibitor [Nω-nitro-l-arginine methyl ester (L-NAME)] treatment abolished the above effects and decreased phosphorylation of eNOS, but not Akt. Conclusions: Collectively, the results demonstrate that LIPC ameliorates CM-induced renal vasocontraction and is mediated by activation of PI3K/Akt/eNOS signaling pathway.
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