Retracted: Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Yun-Qian Wang, Cong-Cong Fan, Bao-Ping Chen, Jun Shi. Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway. Med Sci Monit 2017; 23:3897-3903. DOI: 10.12659/MSM.905381.

Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte.

Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine-derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA-16-5p (miR-16-5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR-16-5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual-luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR-16-5p and promote VEGFA in human podocytes (HPDCs). miR-16-5p in hUSCs was transferred through the exosome pathway to HG-treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR-16-5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG-induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR-16-5p were injected into diabetic rats via tail vein, followed by qualification of miR-16-5p and observation on the changes of podocytes, which revealed that overexpressed miR-16-5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR-16-5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

LncRNA lnc-ISG20 promotes renal fibrosis in diabetic nephropathy by inducing AKT phosphorylation through miR-486-5p/NFAT5.

Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-ß1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.

Scanning Ion Conductance Microscopy: Surface Charge Effects on Electroosmotic Flow Delivery from a Nanopipette.

Scanning ion conductance microscopy (SICM) is a powerful and versatile technique that allows an increasingly wide range of interfacial properties and processes to be studied. SICM employs a nanopipette tip that contains electrolyte solution and a quasi-reference counter electrode (QRCE), to which a potential is applied with respect to a QRCE in a bathing solution, in which the tip is placed. The work herein considers the potential-controlled delivery of uncharged electroactive molecules (solute) from an SICM tip to a working electrode substrate to determine the effect of the substrate on electroosmotic flow (EOF). Specifically, the local delivery of hydroquinone from the tip to a carbon fiber ultramicroelectrode (CF UME) provides a means of quantifying the rate of mass transport from the nanopipette and mapping electroactivity via the CF UME current response for hydroquinone oxidation to benzoquinone. EOF, and therefore species delivery, has a particularly strong dependence on the charge of the substrate surface at close nanopipette-substrate surface separations, with implications for retaining neutral solute within the tip predelivery and for the delivery process itself, both controlled via the applied tip potential. Finite element method (FEM) simulations of mass transport and reactivity are used to explain the experimental observations and identify the nature of EOF, including unusual flow patterns under certain conditions. The combination of experimental results with FEM simulations provides new insights on mass transport in SICM that will enhance quantitative applications and enable new possibilities for the use of nanopipettes for local delivery.

Thiomicrorhabdus sediminis sp. nov. and Thiomicrorhabdus xiamenensis sp. nov., novel sulfur-oxidizing bacteria isolated from coastal sediments and an emended description of the genus Thiomicrorhabdus.

Two novel Gram-strain-negative and rod-shaped bacteria, designated strain G1T and G2T, were isolated from sediment samples collected from the coast of Xiamen, PR China. The cells were motile by a single polar flagellum. Growth of strain G1T occurred at 10-40 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 7.5) and with 5-1530 mM NaCl (optimum, 510 mM), while the temperature, pH and NaCl concentration ranges for G2T were 4-45 °C (optimum, 28 °C), pH 5.5-8.0 (optimum, pH 6.5) and 85-1530 mM NaCl (optimum, 340 mM). The two isolates were obligate chemolithoautotrophs capable of using thiosulfate, sulfide, elemental sulphur or tetrathionate as an energy source. Strain G1T used molecular oxygen or nitrite as an electron acceptor, while strain G2T used molecular oxygen as the sole electron acceptor. The dominant fatty acids of G1T and G2T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16 : 0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The DNA G+C content of G1T and G2T were 45.1 and 48.3 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain G1T and G2T were members of the genus Thiomicrorhabdus, and most closely related to Thiomicrorhabdus hydrogeniphila MAS2T (96.0 %) and Thiomicrorhabdus indica 13-15AT (95.4 %), respectively. The 16S rRNA gene sequence similarity between strains G1T and G2T was 95.8 %. Based on the phylogenetic, genomic and phenotypic data presented here, the isolate strains represent novel species of the genus Thiomicrorhabdus, for which the names Thiomicrorhabdus sediminis sp. nov. (type strain G1T=MCCC 1A14511T=KCTC 15841T) and Thiomicrorhabdus xiamenensis sp. nov. (type strain G2T=MCCC 1A14512T=KCTC 15842T) are proposed.

Scanning Ion Conductance Microscopy: Quantitative Nanopipette Delivery-Substrate Electrode Collection Measurements and Mapping.

Scanning ion conductance microscopy (SICM) is becoming a powerful multifunctional tool for probing and analyzing surfaces and interfaces. This work outlines methodology for the quantitative controlled delivery of ionic redox-active molecules from a nanopipette to a substrate electrode, with a high degree of spatial and temporal precision. Through control of the SICM bias applied between a quasi-reference counter electrode (QRCE) in the SICM nanopipette probe and a similar electrode in bulk solution, it is shown that ionic redox species can be held inside the nanopipette, and then pulse-delivered to a defined region of a substrate positioned beneath the nanopipette. A self-referencing hopping mode imaging protocol is implemented, where reagent is released in bulk solution (reference measurement) and near the substrate surface at each pixel in an image, with the tip and substrate currents measured throughout. Analysis of the tip and substrate current data provides an improved understanding of mass transport and nanoscale delivery in SICM and a new means of synchronously mapping electrode reactivity, surface topography, and charge. Experiments on Ru(NH3)63+ reduction to Ru(NH3)62+ and dopamine oxidation in aqueous solution at a carbon fiber ultramicroelectrode (UME), used as the substrate, illustrate these aspects. Finite element method (FEM) modeling provides quantitative understanding of molecular delivery in SICM. The approach outlined constitutes a new methodology for electrode mapping and provides improved insights on the use of SICM for controlled delivery to interfaces generally.

Differential-Concentration Scanning Ion Conductance Microscopy.

Scanning ion conductance microscopy (SICM) is a nanopipette-based scanning probe microscopy technique that utilizes the ionic current flowing between an electrode inserted inside a nanopipette probe containing electrolyte solution and a second electrode placed in a bulk electrolyte bath, to provide information on a substrate of interest. For most applications to date, the composition and concentration of the electrolyte inside and outside the nanopipette is identical, but it is shown herein that it can be very beneficial to lift this restriction. In particular, an ionic concentration gradient at the end of the nanopipette, generates an ionic current with a greatly reduced electric field strength, with particular benefits for live cell imaging. This differential concentration mode of SICM (ΔC-SICM) also enhances surface charge measurements and provides a new way to carry out reaction mapping measurements at surfaces using the tip for simultaneous delivery and sensing of the reaction rate. Comprehensive finite element method (FEM) modeling has been undertaken to enhance understanding of SICM as an electrochemical cell and to enable the interpretation and optimization of experiments. It is shown that electroosmotic flow (EOF) has much more influence on the nanopipette response in the ΔC-SICM configuration compared to standard SICM modes. The general model presented advances previous treatments, and it provides a framework for quantitative SICM studies.

Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway.

BACKGROUND Resistin-like molecule beta (RELM-ß) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-ß in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-ß in the primitive development of DN via MAPK signaling pathways. MATERIAL AND METHODS Lentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-ß up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting. RESULTS The HMCs with up-regulated and down-regulated expression of RELM-ß increased or decreased significantly at 2-3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-ß protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-ß. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-ß. Up-regulated expression of RELM-b induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway. CONCLUSIONS The results provide evidence that RELM-b is a potential molecular target for the treatment of DN.

Pathogen distribution and drug resistance of nephrology patients with urinary tract infections.

OBJECTIVE: Pathogen distribution characteristics of nephrology patients with urinary tract infections are studied, and drug resistance of nephrology and urinary tract infection disease are analyzed, so as to provide sufficient evidence for treatment of patients. METHODS: Conduct randomized control study of 3500 cases of nephrology patients with urinary tract infections treated in different hospitals from December 2013 to December 2015, isolate pathogens in patients' urine samples, perform identification and drug sensitive test and then conduct detailed analysis of drug resistance of pathogens. RESULTS: Through isolation of pathogens, it can be found that all pathogens include Escherichia coli, Gram-positive cocci, gram-negative bacteria, fungi, Acinetobacter baumannii, Enterococcus faecalis, and urinary Enterococcus. Among them, proportion of E. coli is the largest. Patients have relatively high drug resistance to ceftriaxone, gentamicin, ciprofloxacin and cotrimoxazole. CONCLUSION: For nephrology patients with urinary tract infection, the main pathogen is E. coli, which has had some drug resistance. Drug resistance detection of pathogen should be strengthened in clinics, so as to provide strong guidance for clinical treatment and promote effective treatment of patients.

[Roles of KLF5 in inhibition TNFα-induced SK-BR-3 breast cancer cell apoptosis].

OBJECTIVE: To explore the expression levels and roles of Krüpple-like factor 5 (KLF5) in tumor necrosis factor α (TNFα)-induced SK-BR-3 breast cancer cells. METHODS: SK-BR-3 breast cancer cells were stimulated by TNFα at different concentrations (0, 1, 5, 10, 20 µg/L) for specified durations (0, 6, 12, 24, 36 h). Western blot was performed to detect KLF5 protein levels. Then Western blot and quantitative real-time PCR (qRT-PCR) were used to detect the expression levels of apoptosis genes. Flow cytometry and qRT-PCR were used to observe the effects of exogenous KLF5 on TNFα-induced apoptosis of SK-BR-3 breast cancer cell. RESULTS: KLF5 expression levels significantly decreased in TNFα-stimulated SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Quantitative RT-PCR results showed that TNFα up-regulate apoptosis gene caspase 3, caspase 9 and bax expression levels and down-regulate bcl-1 level in SK-BR-3 cells. Adenovirus expression vectors of pAd-GFP and pAd-GFP-KLF5 were constructed and used to infect SK-BR-3 breast cancer cells. Over-expression of GFP-KLF5 inhibited apoptosis in TNFα-stimulated SK-BR-3 breast cancer cells. CONCLUSION: TNFα reduces KLF5 expression in SK-BR-3 breast cancer cells and KLF5 participates in TNFα-induced SK-BR-3 cell apoptosis.

[Expressions of immunogenic molecules in low-dose radiotherapy-treated human renal clear cell carcinoma 786-0 cells].

OBJECTIVE: To explore the effects of low-dose radiation on the expression of immunogenic membrane molecules calreticulin (CRT) and MHC-I/II on the surface of human renal clear cell carcinoma 786-0 cells. METHODS: The inhibitory activity of low-dose radiation on cell line 786-0 was examined by CCK-8 assay. And the post-radiation membrane expressions of CRT, MHC-I and MHC-II were measured by flow cytometry while CRT was visualized by immunofluorescence photography. RESULTS: The inhibition rates on the proliferative capacities of four 786-0 cell lines rose with the incremental radiation doses of 0, 6, 12 and 24 Gy. And the CRT expression levels of each experimental group was significantly higher than that of the control group (P < 0.001). Along with incremental doses of irradiation, the average calreticulin fluorescence intensities increased gradually initially and then there was a downward trend. The membrane expressions of MHC-I and MHC-II of each experimental group was significantly higher than those of the control group (P < 0.05). As the irradiation dose increased, the average MHC-I fluorescence intensities increased gradually in a dose-dependent manner. CONCLUSION: The low-dose radiotherapy may up-regulate CRT and MHC class I/II related with the immunogenicity of tumor cells to induce immune response against tumors.

Construction of Sports Nutrition Dynamic Intervention Mechanism Based on the Improvement of College Students' Physical Health.

Exercise can improve people's physical health and strengthen their body bones. But the physique of college students is generally too poor. The enhancement of College Students' physique cannot be completed in a day. This study aims to explore the best sports nutrition intervention scheme for strengthening college students' physique from the construction of sports nutrition dynamic intervention mechanism, so as to provide theoretical reference for public physical education teaching and students' independent exercise. In this study, 100 full-time associate students in our university were selected as the research objects. Before the experiment, the subjects' body shape, body function, and physical quality were tested. Based on the random mathematical method, the full-time associate students were randomly divided into four groups: control group, exercise intervention group, nutrition intervention group, and sports nutrition intervention group, with 25 people in each group. After the experiment, the body shape, body function, and physical quality of the four groups were tested. The results show that exercise and nutrition intervention have little effect on college students' height, but have great influence on body mass index, vital capacity and 800 meter running. Especially after the experiment, the vital capacity of the exercise group and the sports nutrition group increased by nearly 250 ml and 500 ml, respectively, and the 800 m running time increased by nearly 10 s and 18 s, respectively. Strengthening exercise and increasing nutritional intake can effectively improve the institutional health of college students.

A Malicious Domain Detection Model Based on Improved Deep Learning.

With the rapid development of the Internet, malicious domain names pose more and more serious threats to many fields, such as network security and social security, and there have been many research results on malicious domain detection. This article proposes a malicious domain name detection model based on improved deep learning, which can combine the advantages of three different network models, convolutional neural network (CNN), temporal convolutional network (TCN), and long short-term memory network (LSTM) in malicious domain name detection, to obtain a better detection effect than that of the original single or two models. Experiments show that the effect of the improved deep learning model proposed in this article is better than that of the combined model of CNN and LSTM or the combined model of CNN and TCN, and the accuracy and regression rates reached 99.76% and 98.81%, respectively.

Artificial Synapse: Spatiotemporal Heterogeneities in Dopamine Electrochemistry at a Carbon Fiber Ultramicroelectrode.

An artificial synapse is developed that mimics ultramicroelectrode (UME) amperometric detection of single cell exocytosis. It comprises the nanopipette of a scanning ion conductance microscope (SICM), which delivers rapid pulses of neurotransmitter (dopamine) locally and on demand at >1000 defined locations of a carbon fiber (CF) UME in each experiment. Analysis of the resulting UME current-space-time data reveals spatiotemporal heterogeneous electrode activity on the nanoscale and submillisecond time scale for dopamine electrooxidation at typical UME detection potentials. Through complementary surface charge mapping and finite element method (FEM) simulations, these previously unseen variations in electrochemical activity are related to heterogeneities in the surface chemistry of the CF UME.

Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC. METHODS: Correlation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo. RESULTS: PTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo. CONCLUSION: This study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.

[Retracted] MicroRNA­21 promotes the progression of peritoneal fibrosis through the activation of the TGF­ß/Smad signaling pathway: An in vitro and in vivo study.

Int J Mol Med 41: [Related article:] 1030­1038, 2018; DOI: 10.3892/ijmm.2017.3268. An interested reader drew to our attention the fact that the western blots featured in Fig. 2B in the above article contained duplicated data: The data shown for the TGF­ß and vimentin protein bands were apparently identical; furthermore, there was a strong likelihood that the protein bands featured for the ZO­1 and SMAD­3 experiments were also the same, but flipped horizontally relative to the other. Following an investigation, the Journal was able to confirm that this duplication of the research data had probably occurred. On those grounds, the Editor of International Journal of Molecular Medicine has decided that the above paper should be retracted. We were unable to make contact with the authors of the article published in International Journal of Molecular Medicine, despite every effort to do so. The Editor deeply regrets any inconvenience that this retraction has caused to the the readership of the Journal.

Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition.

Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications. However, the role of FOXO6 in diabetic nephropathy (DN) has not been fully understood. In the present study, we evaluated the functions of FOXO6 in high glucose (HG)-induced glomerular mesangial cells (MCs). The results showed that FOXO6 expression was significantly elevated in MCs after HG stimulation. Knockdown of FOXO6 by transfection with small interfering RNA (siRNA) targeting FOXO6 (siRNA-FOXO6) suppressed cell proliferation in MCs. The productions of extracellular matrix (ECM) components including collagen IV (Col IV) and fibronectin (FN) were markedly decreased after FOXO6 knockdown in MCs. Furthermore, knockdown of FOXO6 inhibited HG-induced activation of p38 MAPK signaling pathway in MCs. Collectively, these findings suggested that knockdown of FOXO6 inhibited cell proliferation and ECM accumulation in HG-induced MCs via inhibiting p38 MAPK signaling pathway. FOXO6 might be a beneficial therapeutic target for the prevention and treatment of DN.

Retracted Article: TMEM88 inhibits fibrosis in renal proximal tubular epithelial cells by suppressing the transforming growth factor-ß1/Smad signaling pathway.

Transmembrane protein 88 (TMEM88) belongs to a member of the TMEM family, and was reported to be involved in fibrogenesis. However, the biological role of TMEM88 in renal fibrosis has not been elucidated. Therefore, the objective of this study was to investigate the effect of TMEM88 on cell proliferation and extracellular matrix (ECM) accumulation in a TGF-ß1-induced human renal proximal tubular epithelial cell line (HK2). Our results showed that TMEM88 was downregulated in renal fibrotic tissues and TGF-ß1-treated HK2 cells. In addition, TMEM88 overexpression inhibited TGF-ß1-induced cell proliferation and migration in HK2 cells. Furthermore, TMEM88 overexpression reduced the production of α-SMA, collagen I, and collagen III in TGF-ß1-stimulated HK2 cells. Mechanistically, TMEM88 overexpression suppressed the phosphorylation status of Smad2 and Smad3 in TGF-ß1-stimulated HK2 cells. In conclusion, data from our experiments demonstrate that TMEM88 plays a pivotal role in the pathological process of renal fibrosis. TMEM88 inhibited fibrosis in renal proximal tubular epithelial cells by suppressing the TGF-ß1/Smad signaling pathway.

Silencing of PAQR3 suppresses extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via PI3K/AKT signaling pathway.

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism. Our results demonstrated that HG significantly up-regulated the expression of PAQR3 in human MCs. In addition, knockdown of PAQR3 efficiently suppressed MC proliferation and ECM production in HG-stimulated MCs. Furthermore, knockdown of PAQR3 markedly reversed HG-induced PI3K/AKT activation in MCs. In summary, our present study demonstrated that knockdown of PAQR3 suppressed HG-induced the proliferation and ECM accumulation in human MCs, via inhibiting the PI3K/AKT signaling pathway. Thus, PAQR3 may be a potential therapeutic target for the treatment of diabetic nephropathy.

miR-182 enhances acute kidney injury by promoting apoptosis involving the targeting and regulation of TCF7L2/Wnt/ß-catenins pathway.

Acute kidney injury (AKI) is a sudden decay in renal function leading to increasing morbidity and mortality. miR-182 has been reported to be actively involved in kidney diseases. However, the function and molecular mechanism of miR-182 in AKI still need to be elucidated. The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urine Kim-1 in I/R-induced rat AKI model were detected by a Beckman Autoanalyzer. miR-182 and transcription factor 7-like-2 (TCF7L2) mRNA expression were measured by qRT-PCR. Flow cytometry and caspase-3 colorimetry analysis were performed to determine NRK-52E cell apoptosis. Bioinformatics and dual-luciferase reporter were used to identify the interaction between miR-182 and TCF7L2. miR-182 expression was increased in both I/R-induced rat models and hypoxia-treated NRK-52E cells, and miR-182 overexpression stimulated the apoptosis of hypoxia-induced NRK-52E cells. Dual-luciferase analysis disclosed that TCF7L2 was a target of miR-182. TCF7L2 suppressed hypoxia-induced apoptosis in NRK-52E cells, and the inhibitory effect of TCF7L2 on cell apoptosis could be reversed with miR-182 restoration. Moreover, the activity of Wnt/ß-catenin signaling pathway was promoted following overexpression of TCF7L2 in NRK-52E cells with hypoxia treatment, and this effect was greatly attenuated by the increased miR-182 expression. Finally, in vivo experiment also validated the alleviation of miR-182 inhibitor on I/R-induced kidney injury and apoptosis via regulating TCF7L2/ Wnt/ß-catenin pathway. miR-182 exacerbated AKI involving the targeting and regulation of TCF7L2/Wnt/ß-catenin signaling, unveiling a novel regulatory pathway in ischemia-reperfusion injury and elucidating a potential biomarker for AKI treatment.