Acute kidney injury (AKI) is a common kidney disorder that affects public health and the incidence of AKI. Sepsis, acute ischemia or hypoxia is the main reason for the occurrence of AKI. Recently, noncoding RNA that include microRNA and long noncoding RNA (lncRNAs) were reported to play important roles in AKI as well as have the potential to serve as a biomarker or therapeutic target for the development of the diagnostic and prognostic strategies of AKI. In the current study, we aimed to investigate the expression and biological function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in ischemia‐induced AKI in patients' sample and in vitro. The expressions of NEAT1 and miR‐27a‐3p in ischemia/reperfusion‐induced AKI patients were examined by quantitative reverse transcription polymerase chain reaction. Cell injury was induced by treatment of human kidney tubular cells (HK‐2) with CoCl2. After treatment, the influences of NEAT1 and miR‐27a‐3p on the cell apoptosis in the CoCl2‐stimulated HK‐2 were tested by flow cytometry. The flow analysis results showed that the expression of NEAT1 was markedly higher in the ischemia‐induced AKI patients compared with normal control. Moreover, repression the expression of NEAT1 decreased CoCl2‐induced injury in HK‐2. The expression of miR‐27a‐3p was negatively regulated by NEAT1. Inhibition the expression of NEAT1 attenuated overexpression of miR‐27a‐3p enhanced CoCl2‐induced injury. In summary, an ischemia‐induced injury may be enhanced by a high level of NEAT1 through targeting miR‐27a‐3p. Thus, NEAT1 has the potential to be explored as a biomarker for diagnosis and target for therapeutic strategies in ischemia‐induced AKI.
Context: Curcumin could ameliorate diabetic nephropathy (DN), but the mechanism remains unclear.Objective: The efficacy of curcumin on epithelial-to-mesenchymal transition (EMT) of podocyte and autophagy in vivo and in vitro was explored.Materials and methods: Thirty male Sprague–Dawley rats were divided into the normal, model and curcumin (300 mg/kg/d, i.g., for 8 weeks) groups. Rats received streptozotocin (50 mg/kg, i.p.) and high-fat-sugar diet to induce DN. Biochemical indicators and histomorphology of renal tissues were observed. In addition, cultured mouse podocytes (MPC5) was induced to EMT with serum from DN rats, and then exposed to curcumin (40 µM) with or without fumonisin B1, an Akt specific activator or 3BDO, the mTOR inducer. Western blot analysed the levels of EMT and autophagy associated proteins.Results: Administration of curcumin obviously reduced the levels of blood glucose, serum creatinine, urea nitrogen and urine albumen (by 28.4, 37.6, 33.5 and 22.4%, respectively), and attenuated renal histomorphological changes in DN rats. Podocytes were partially fused and autophagic vacuoles were increased in curcumin-treated rats. Furthermore, curcumin upregulated the expression of E-cadherin and LC3 proteins and downregulated the vimentin, TWIST1, p62, p-mTOR, p-Akt and P13K levels in DN rats and MPC5 cells. However, fumonisin B1 or 3BDO reversed the effects of curcumin on the expression of these proteins in cells.Discussion and conclusions: The protection against development of DN by curcumin treatment involved changes in inducing autophagy and alleviating podocyte EMT, through the PI3k/Akt/mTOR pathway, providing the scientific basis for further research and clinical applications of curcumin.
Our modified laparoscopic intra-abdominal fixation technique using suture passer hernia forceps is a simple and safe method for PD catheter placement and is effective in minimizing the risk of catheter migration.
Background Podocyte injury, characterized by podocyte hypertrophy, apoptosis, and epithelial‐mesenchymal transition (EMT), is the major causative factor of diabetic nephropathy (DN). Autophagy dysfunction is regarded as the major risk factor for podocyte injury including EMT and apoptosis. High mobility group box 1 (HMGB1) is involved in the progression of DN through the induction of autophagy. However, the underlying mechanism remains unknown. Methods Plasma HMGB1 concentrations were determined in DN patients using ELISA. Apoptosis of DN serum‐treated podocytes was evaluated by flow cytometry. Podocyte autophagy flux was measured using immunofluorescence. Western blotting analysis was used to investigate HMGB1 expression, EMT, and autophagy‐related signaling pathways. Results Upregulation of HMGB1 was found in DN patients and DN serum‐treated podocytes. Removal of HMGB1 inhibited DN serum‐mediated podocyte apoptosis by inhibiting autophagy and activating AKT/mammalian target of rapamycin (mTOR) signaling. In addition, HMGB1 depletion repressed the progression of podocyte EMT by inhibiting transforming growth factor (TGF)‐β/smad1 signaling in vitro and in vivo. The combination of HMGB1 short interference (si) RNA and the autophagy activator rapamycin protected against podocyte apoptosis and EMT progression by inhibiting the AKT/mTOR and TGF‐β/smad signaling pathway, respectively. Conclusions Although HMGB1 siRNA and rapamycin treatment had opposite effects on autophagy and AKT/mTOR signaling, there was no contradiction about the role of HMGB1 siRNA and rapamycin on AKT/mTOR pathway because autophagy and AKT/mTOR signaling play dual roles in intracellular biological processes. Based on the findings of this study, we may assume that HMGB1‐initiated autophagy is harmful, whereas rapamycin is beneficial to podocyte survival. Possibly combined treatment with HMGB1 siRNA and rapamycin improved podocyte damage and EMT by regulating autophagy homeostasis.
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