Chlorogenic acid (CGA), a polyphenolic compound, exists widely in medicinal herbs, which has been shown a strong antioxidant and anti-inflammatory effect. This study investigated the protective effects and mechanism of CGA on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Treatment of CGA successfully ameliorates LPS-induced renal function and pathological damage. Moreover, CGA dose-dependently suppressed LPS-induced blood urea nitrogen (BUN), creatinine levels, and inflammatory cytokines TNF-α, IL-6, and IL-1β in serum and tissue. The relative proteins' expression of TLR4/NF-κB signal pathway was assessed by western blot analysis. Our results showed that CGA dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. CGA also suppressed LPS-induced TNF-α, IL-6, and IL-1β production both in serum and kidney tissues. Furthermore, our results showed that CGA significantly inhibited the LPS-induced expression of phosphorylated NF-κB p65 and IκB as well as the expression of TLR4 signal. In conclusion, our results provide a mechanistic explanation for the anti-inflammatory effects of CGA in LPS-induced AKI mice through inhibiting TLR4/NF-κB signaling pathway.

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1 ΔHBS , which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1 ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1 WT ) in renal tissues. RNA-seq analysis revealed that FGF1 ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1 ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1 ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3β/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1 ΔHBS . This finding expands the potential uses of FGF1 ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.

New Findings What is the central question of this study?What is the role of the long non‐coding RNA X‐inactive specific transcript (XIST), which is up‐regulated in injured podocytes and membranous nephropathy, in the pathogenesis of membranous nephropathy? What is the main finding and its importance?XIST was up‐regulated in kidney tissue with membranous nephropathy and in injured podocytes. Down‐regulation of XIST inhibited podocyte apoptosis. XIST negatively regulated miR‐217, and miR‐217 modulated Toll‐like receptor 4. Inhibition of XIST suppressed podocyte apoptosis induced by angiotensin II via miR‐217. Abstract Membranous nephropathy is often characterized by glomerular podocyte injury. Up‐regulation of the long non‐coding RNA (lncRNA) X‐inactive specific transcript (XIST) has been verified in membranous nephropathy and in injured podocytes. Here the role of XIST in podocyte injury and membranous nephropathy was explored. Quantitative real‐time PCR and western blot were performed to detect the expression of XIST and miR‐217, and Toll‐like receptor 4 (TLR4) protein, respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR‐217 was analysed by RNA immunoprecipitation and RNA pull‐down assay. A dual luciferase reporter assay was used to examine the interplay between miR‐217 and TLR4. Up‐regulation of the lncRNA XIST and angiotensin II (Ang II) and kidney and podocyte injury were indicated in kidney tissue of patients with membranous nephropathy. Increase of XIST and apoptosis were induced by Ang II in podocytes. Down‐regulation of XIST reversed podocyte apoptosis induced by Ang II. MiR‐217 was negatively regulated by XIST. MiR‐217 controlled TLR4 by targeting its 3′‐untranslated region. XIST modulated TLR4 through miR‐217 and inhibition of XIST reduced podocyte apoptosis induced by Ang II via regulating miR‐217. Down‐regulation of XIST ameliorates podocyte apoptosis via the miR‐217–TLR4 pathway, which may improve membranous nephropathy.

BackgroundAn association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy (IgAN) remains controversial.MethodsWe conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN. Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from the Second Affiliated Hospital of Wenzhou Medical College, China, and various parameters were documented during follow-up until 2015. The definition of the primary endpoint was a decrease of estimated glomerular filtration rate (eGFR) more than 30% from their baseline levels.ResultsA total of 403 patients (55.3% female, average 33.7 months of follow-up) were identified and enrolled, with the primary endpoint occurring in 39 (9.8%) patients. Among the patients selected, 202 (50.1%) received corticosteroid treatment alone or in combination with another immunosuppressant (GS group), while others did not receive immunosuppressive treatment (non-GS group). The incidence of the primary endpoint was slightly lower in the GS group compared to the non-GS group (7.0% versus 12.6%, p = 0.06). Multivariate Cox proportional-hazard regression analyses, adjusting for age, systolic and diastolic blood pressure, 24-h urine protein, and immunosuppressive therapy, showed that serum complement 4 (C4) levels (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.8, p < 0.001) and serum complement 3 (C3) levels (HR 0.6, 95% CI 0.2-0.6, p < 0.001) were significantly associated with a poor prognosis among patients with IgAN.ConclusionsWe demonstrated that an increase in serum C4, as well as a decrease in C3, was an important outcome determinant for patients with IgAN. Testing serum C3 and C4 levels might assist in predicting renal outcomes among these patients.

Background/Aims: Acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), is associated with decreased survival and increased progression of chronic kidney disease. A barrier to improving the clinical outcomes is the incomplete understanding of the pathogenesis of AKI. Our objective is to test the hypothesis that intrarenal renin-angiotensin system (RAS) is overexpressed in patients with ATN and could be an indicator of ATN severity. Methods: A transversal study was conducted in patients with biopsy-proven ATN. Intrarenal expression of angiotensinogen and angiotensin II, and urinary angiotensinogen were measured. Results: Patients with ATN demonstrated upregulation of intrarenal RAS, evidenced by upregulation of intrarenal angiotensinogen and angiotensin II. Patients with ATN also have elevated urinary angiotensinogen level that correlated with the overexpressed intrarenal RAS. Moreover, this increase in intrarenal RAS expression and urinary angiotensinogen was associated with the extent of acute tubular injury and urinary albumin excretion, respectively. Conclusions: We demonstrate that the intrarenal RAS is upregulated in patients with ATN and is associated with the severity of ATN. Urinary angiotensinogen reflects intrarenal RAS status, and is of value to assess the severity of ATN.