Lin Sun

The Second Xiangya Hospital of Central South University, Ch’ang-sha-shih, Hunan, China

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Publications (91)245.15 Total impact

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    ABSTRACT: We report the outcome of a 52-year-old patient with diabetic nephropathy and receiving maintenance hemodialysis (HD) using low molecular weight heparin (LMWH) as an anticoagulant for 2 years. He presented right lower limb pain accompanied with difficulty in walking for 2 months, and had no history of bleeding tendency or trauma. Physical examination revealed marked swelling and tenderness on his right lower limb. By ultrasound and magnetic resonance imaging (MRI) diagnoses, the calf hematoma was diagnosed and identified with venous thrombosis. Following treatment with heparin-free HD, the swelling regressed and pain subsided, and a follow-up MRI showed complete dissolution of hematoma. However, similar symptoms recurred in the right upper limb after 2 months without any predisposition, he was just placed on HD with LMWH, and symptoms regressed following the aforementioned therapy. This suggests that HD patients, especially with diabetic nephropathy having extremity hematoma, should be watched for the development of spontaneous hemorrhage that can be differentially diagnosed by imaging tests, such as MRI, and can be effectively treated with heparin-free HD.
    Hemodialysis International 12/2014; · 1.44 Impact Factor
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    ABSTRACT: Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondrial injury. Myo-inositol oxygenase (MIOX), a tubular-specific enzyme, modulates redox imbalance and apoptosis in tubular cells in diabetes, but these mechanisms remain unclear. We investigated the role of MIOX in perturbation of mitochondrial quality control, including mitochondrial dynamics and autophagy/mitophagy, under high-glucose (HG) ambience or a diabetic state. HK-2 or LLC-PK1 cells subjected to HG exhibited an upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which coincided with increased reactive oxygen species generation, Bax activation, cytochrome C release, and apoptosis. Overexpression of MIOX in LLC-PK1 cells enhanced the effects of HG, whereas MIOX siRNA or d-glucarate, an inhibitor of MIOX, partially reversed these perturbations. Moreover, decreasing the expression of MIOX under HG ambience increased PTEN-induced putative kinase 1 expression and the dependent mitofusin-2-Parkin interaction. In tubules of diabetic mice, increased MIOX expression and mitochondrial fragmentation and defective autophagy were observed. Dietary supplementation of d-glucarate in diabetic mice decreased MIOX expression, attenuated tubular damage, and improved renal functions. Notably, d-glucarate administration also partially attenuated mitochondrial fragmentation, oxidative stress, and apoptosis and restored autophagy/mitophagy in the tubular cells of these mice. These results suggest a novel mechanism linking MIOX to impaired mitochondrial quality control during tubular injury in the pathogenesis of DKD and suggest d-glucarate as a potential therapeutic agent for the amelioration of DKD.
    Journal of the American Society of Nephrology : JASN. 09/2014;
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    ABSTRACT: The diabetic milieu is believed to change the activity, or result in damage of podocytes - a key component of the glomerular filtration barrier and known to secrete matrix for glomerular basement membrane. This in turn contributes to diabetic nephropathy. However, how podocyte dysfunction is triggered in diabetic nephropathy remains ambiguous. Galectin-1 belongs to Galectin family that bind to β-galactoside residues of glycosylated proteins. We explored whether Galectin-1 is dysregulated in diabetic nephropathy using 3 different techniques, namely real-time polymerase chain reaction, western blotting and immunofluorescent staining, to follow the expression of Galectin-1 under high glucose levels in podocytes. High glucose consistently induced Galectin-1 expression. Immunohistochemistry using a Galectin-1-specific antibody also showed elevated Galectin-1 in renal tissues of diabetic patients with manifestation of nephropathy, indicating a correlation of Galectin-1 overexpression with diabetic nephropathy. Upregulation of Galectin-1 is associated with loss of podocin, which is important for the physiological function of podocytes and decreases in the renal tissues of diabetic nephropathy. Increased Galectin-1 is a causal event for the high glucose-induced loss of podocin, since silencing Galectin-1 in podocytes increased podocin expression in the presence of 25 mM glucose. Thus expression of Galectin-1 in diabetic nephropathy may serve as a marker and contribute to disease progression by interfering with podocin expression.
    Cell Biology International 09/2014; · 1.64 Impact Factor
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    ABSTRACT: Bacterial peritonitis is serious disease and remains a diagnostic challenge for clinicians. Many studies have highlighted the potential usefulness of procalcitonin(PCT) for identification of bacterial peritonitis, however, the overall diagnostic value of PCT remains unclear. Therefore, we performed a meta-analysis to assess the accuracy of PCT for detection of bacterial peritonitis.
    BMC Infectious Diseases 08/2014; 14(1):452. · 3.03 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy in humans and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy.
    Current Medicinal Chemistry 07/2014; · 3.72 Impact Factor
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    ABSTRACT: A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.
    Annals of Saudi medicine 05/2014; 34(3):257-61. · 1.10 Impact Factor
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    ABSTRACT: Emerging evidence has suggested that human peritoneal mesothelial cells (HPMCs) undergo epithelial‑mesenchymal transition (EMT) in peritoneal fibrosis. The molecular mechanisms underlying peritoneal fibrosis and the key molecules involved are not yet fully elucidated. In order to enhance the understanding of peritoneal fibrosis, the present study investigated the roles of integrin‑linked kinase (ILK) and glycogen synthase kinase 3β (GSK‑3β) in high glucose‑induced phenotypic alterations of HPMCs. It was observed that HPMCs exhibited a cobblestone morphology under normal glucose conditions, whereas under high glucose conditions they had a spindle morphology. Additionally, under high glucose conditions it was found that E‑cadherin expression was decreased and vimentin expression was increased in HPMCs, suggesting HPMCs underwent EMT. ILK expression in high glucose conditions was also increased in a dose‑ and time‑dependent manner. The role of ILK in the induction of EMT in HPMCs was further investigated using small interfering RNA (siRNA). Following knockdown of ILK gene expression by siRNA, low vimentin expression as well as high E‑cadherin expression were observed, suggesting that EMT was inhibited. ILK‑knockdown also inhibited phosphorylation of GSK‑3β. These results indicate that ILK‑knockdown inhibits EMT of HPMCs through inhibition of GSK‑3β phosphorylation. These findings suggest that ILK may be used as a novel diagnostic and therapeutic target for HPMC fibrosis in the future.
    Molecular Medicine Reports 04/2014; · 1.17 Impact Factor
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    ABSTRACT: Abstract Background: Vitamin E-coated dialyzer may have an effect on oxidative stress and inflammation status in hemodialysis (HD) patients. Therefore, we performed a systematic review to assess the anti-oxidation and anti-inflammatory effects of vitamin E-coated dialyzer in HD patients. Methods: The randomized controlled trials (RCTs) and quasi-RCTs of vitamin E-coated dialyzer versus conventional dialyzer for HD patients were searched from multiple databases. We screened relevant studies according to predefined inclusion criteria and performed meta-analyses using RevMan 5.1 software. Results: Meta-analysis showed vitamin E-coated dialyzer therapy could significantly decrease the serum thiobarbituric acid reacting substances (TBARS) (SMD, -0.95; 95% CI, -1.28 to -0.61; p < 0.00001), oxLDL (SMD, -0.61; 95% CI, -1.04 to -0.19; p = 0.005), interleukin-6 (IL-6) (SMD, -0.65; 95% CI, -0.97 to -0.32; p < 0.0001) and C-reactive protein (CRP) levels (SMD, -0.46; 95% CI, -0.87 to -0.05; p = 0.03) compared with that of the control group. However, vitamin E-coated dialyzer did not result in increasing the total antioxidant status (TAS) (SMD, 0.23; 95% CI, -0.16 to 0.61; p = 0.25) and the fractional clearance of urea index (Kt/v) levels (MD, -0.07; 95% CI, -0.14 to 0.00; p = 0.06), in addition, there was no significant difference in plasma superoxide dismutase (SOD) level compared with that of the conventional dialyzer & oral vitamin E group (SMD, 0.28; 95% CI, -0.20 to 0.75; p = 0.26). Conclusions: Vitamin E-coated dialyzer can reduce the oxidative stress and inflammation status reflected by the decreasing of serum TBARS, oxLDL, CRP, and IL-6 levels, and this new dialyzer does not affect the dialysis adequacy.
    Renal Failure 02/2014; · 0.94 Impact Factor
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    ABSTRACT: Besides glomerulus tubulo-interstitium is often concomitantly affected in certain diseases, e.g., diabetic nephropathy, and activation of renin-angiotensin system, to a certain extent, worsens its outcome because of perturbations in hemodynamics and possibly tubulo-glomerular feedback. Certain studies suggest that pathobiology of tubulo-interstitial is influenced by small GTPases, e.g., Rap1. We investigated effect of Ang II on inflammatory cytokines, while at the same time focusing on upstream effector of Rap1, i.e., Epac1, and some of the downstream tubular transport molecules, i.e., NHE3. Ang II treatment of LLC-PK1 cells decreased Rap1a GTPase activity in a time- and dose-dependent manner. While Ang II treatment led to an increased membrane translocation of NHE3, which was reduced with Epac1 and PKA activators. Ang II-induced NHE3 translocation was notably reduced with transfection of Rap1a dominant positive mutants, i.e., Rap1a-G12V or Rap1a-T35A. While transfection of cells with dominant negative Rap1a mutants, i.e., Rap1a-S17A, or with Epac1 mutant, i.e., EPAC-ΔcAMP, normalized the Ang II-induced translocation of NHE3. In addition, Ang II treatment led to an increased expression of inflammatory cytokines, i.e., IL-1β, IL-6, IL-8 and TNF-α, which was reduced with Rap1a-G12V or Rap1a-T35A transfection; while it reverted to previous comparable levels following transfection of Rap1a-S17A or EPAC-ΔcAMP. Ang II-induced expression of cytokines was reduced with the treatment of NHE3 inhibitor, S3226, or with Epac1 and PKA activators. These data suggest that this novel Epac1-Rap1a-NHE3 pathway conceivably modulates the Ang II-induced expression of inflammatory cytokines, and this information may aid in developing strategies to reduce tubulo-intertstitial inflammation in renal diseases.
    AJP Renal Physiology 02/2014; · 4.42 Impact Factor
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    ABSTRACT: To explore tubulointerstitial nephritis antigen (TIN-ag) expression of chronic kidney disease (CKD) patients' renal tissue and the correlation to clinical phenotype. Through digital drawing lots, a total of 77 CKD patients from October 2012 to February 2013 at our department were randomly selected. All of them underwent biopsy. Based upon their pathological findings, they were divided into 2 groups of minimal change disease (MCD) and non-minimal change disease (NMCD). The stains of hematoxylin and eosin and Masson were used to observe renal pathological changes and immunofluorescence for detecting the TIN-ag expression of kidney tissue. The serum levels of creatinine, blood urea nitrogen, estimated glomerular filtration rate (eGFR), 24-hour urine output, 24-hour urine protein, α1-microglobulin, β2-microglobulin, pathological casts, N-acetyl-beta-glucosaminidase (NAG), specific gravity and other clinical parameters were monitored to examine their relationship between renal tissue TIN-ag expression. TIN-ag expression was distinct in renal tubular basement membrane of MCD patients while weak in primary focal segmental glomerulosclerosis (FSGS)(n = 16), IgA nephropathy (n = 23), MN (n = 14) and LN (n = 15) renal tissue. Immunofluorescence quantitative analysis showed that tubular TIN-ag fluorescence intensity of NMCD group was significantly lower than that of MCD group (4.84(3.02, 10.73) vs 20.79(8.19, 37.00), P < 0.01). In addition, TIN-ag expression in renal interstitial collagen area deposition of 0 grade group was higher than that of collagen area deposition 1-3 grades group (all P < 0.05). Serum α1-microglobulin and pathological urine cast, 24-hour urine protein of CKD patients were negatively correlated with kidney tubules TIN-ag expression (r = -0.312, -0.298, -0.214, all P < 0.05). Serum creatinine, blood urea nitrogen, serum β2-microglobulin and eGFR of CKD patients had no significant correlations with TIN-ag expression (P > 0.05). TIN-ag expression of CKD patients with lower expression levels of NAG was significantly higher than that of normal levels of NAG expression. TIN-ag expression of low urine specific gravity group was lower than that of normal urine specific gravity group (P < 0.05). TIN-ag expression of renal tissue tubule basement membrane in NMCD group is significantly lower than that in MCD group. TIN-ag expression is negatively correlated with renal tissue fibrosis. Expression of serum α1-microglobulin and concentrations of urinary pathology tube, 24-hour urine protein, NAG expression and urine specific gravity are negatively correlated with renal tissue TIN-ag expression in CKD patients.
    Zhonghua yi xue za zhi 01/2014; 94(4):246-50.
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    ABSTRACT: The heavy metal lead (Pb) is a major environmental and occupational hazard. Epidemiological studies have demonstrated a strong association between lead exposure and the presence of chronic kidney injury. Some studies have suggested that chelation therapy with calcium disodium ethylenediaminetetraacetic acid (calcium disodium EDTA) might help decrease the progression of chronic kidney disease among patients with measurable body lead burdens. However, calcium disodium EDTA chelation in lead exposure is controversial due to the potential for adverse effects such as acute tubular necrosis. Therefore, we investigated the available randomized controlled trials assessing the renoprotective effects of calcium disodium EDTA chelation therapy. Our meta-analysis shows that calcium disodium EDTA chelation therapy can effectively delay the progression of chronic kidney disease in patients with measurable body lead burdens reflected by increasing the levels of estimated glomerular filtration rate (eGFR) and creatinine clearance rate (Ccr). There appears to be no conclusive evidence that calcium disodium EDTA can decrease proteinuria.
    Nephrology 01/2014; 19(1):56-9. · 1.69 Impact Factor
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    ABSTRACT: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKCδ and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKCδ, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKCδ during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKCδ was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKCδ. Moreover, PKCδ siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKCδ promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient.
    Oxidative medicine and cellular longevity. 01/2014; 2014:746531.
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    ABSTRACT: Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular cells. However, its role and precise mechanism in diabetic nephropathy (DN) in vivo remains unclear. We hypothesize that Rap1 plays a protective role in tubular damage of DN by modulating primarily the mitochondria-derived oxidative stress.The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of tubular cells in DN was examined in rats with Streptozotocin (STZ)-induced diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated technique as well as in renal proximal epithelial tubular cell line (HK-2) exposed to HG ambiance. The results showed that Rap1b expression decreased significantly in tubules of renal biopsies from patients with DN. Over-expression of a constitutively active Rap1b G12V notably ameliorated renal tubular mitochondrial dysfunction, oxidative stress, apoptosis in the kidneys of STZ-induced rats, which was accompanied with increased expression of transcription factor C/EBP-β and PGC-1α. Furthermore, Rap1b G12V also decreased phosphorylation of Drp1, a key mitochondrial fission protein, while boosting the expression of genes related to mitochondrial biogenesis and antioxidants in HK-2 cells induced treated with HG. These effects were imitated by transfection with C/EBP-β or PGC-1α siRNA. In addition, Rap1b could modulate C/EBP-β binding to the endogenous PGC-1α promoter and the interaction between PGC-1α and Catalase or mitochondrial superoxide dismutase. Indicating that Rap1b ameliorates tubular injury and slows the progression of DN by modulation of mitochondrial dysfunction via C/EBP-β:PGC-1α signaling.
    Diabetes 12/2013; · 7.90 Impact Factor
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    ABSTRACT: Objective: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney disease (DKD). Methods: Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin, α-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin, α-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. Results: Tranilast can inhibit the infiltration of mast cells in the kidneys of DKD rats. The expression of α-SMA in the kidneys of DKD rats inereased significantly (P<0.05), while the expression of E-cadherin decreased (P<0.05). Tranilast increased the expression of E-cadherin and decreased the expression of α-SMA in the prophase of DKD dose dependently. The expressions of FN and Col I were increased in the tubulointerstitial fields in DKD model rats (P<0.05). After the tranilast treatment, these changes were relieved to a certein degree (P<0.05). The expression of SCF and c-kit in the tubular and interstitial tissue was slight. The increased expressions of SCF and c-kit protein and mRNA in DKD model rats were downregulated by tranilat (P<0.05). The expressions of SCF and c-kit were positively correlated with the infiltration degree of mast cells and the expressions of FN, Col I. Conclusion: Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the infiltration of mast cells induced by SCF/c-kit pathway.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 12/2013; 38(12):1233-1242.
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    ABSTRACT: Objective: To evaluate the mortality and risk factors for acute kidney injury (AKI) in hospitalized patients by the risk, injury, failure, loss, end stage kidney disease (RIFLE) and acute kidney injury network (AKIN). Methods: We constructed a retrospective study of all AKI patients in the Second Xiangya Hospital of Central South University between February 2006 and January 2011. The diagnosis and classification of AKI were reconfirmed and categorized by RIFLE and AKIN criteria. To compare the clinical characteristics, mortality and associated risk factors in AKI patients by the RIFLE and AKIN stage, univariate analysis and multivariate logistic regression analysis were performed. Results: The patients were diagnosed as AKI by AKIN (n=1027) or by RIFLE criteria (n=1020). There was no significant difference in the hospital mortality, hospital length stay (days), or the proportion of complete recovery in each stage of AKI patients by RIFLE and AKIN (P>0.05). In the univariate analysis, age, pre-renal causes, proportion of hospital acquired AKI, mechanical ventilation, hypotension, the number of failed organs, acute tubular necrosis-index severity score (ATN-ISS), and the peak of serum potassium ion concentration were significantly higher in the non-survivors than in the survivors (P<0.05). Logistic regression analysis revealed that age older than 65, hospital acquired AKI, hypotension, number of failed organs, ATN-ISS scores, and the peak of serum potassium ion concentration were independent risk factors for hospital mortality. Conclusion: Both RIFLE and AKIN criteria have similar scientific value in assessing hospital mortality. AKI stage is associated with the recent prognosis of AKI patients.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 12/2013; 38(12):1243-1252.
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    ABSTRACT: To observe the effect of PKCδ on the phosphorylation of p66Shc and its mitochondrial translocation in human proximal tubular cells (HK-2) under high glucose (HG). HK-2 cells were incubated with different concentrations of D-glucose (5-45 mmol/L) for indicated time (0-48 h). Then the mRNA expressions of PKCδ and p66Shc and the phosphorylation levels of PKCδ (p-PKCδ) and p66Shc (p-p66Shc) were determined by real-time polymerase chain reaction (PCR) and Western blot analysis respectively. In addition, the effect of PKCδ inhibitor on the phosphorylation and mitochondrial translocation of p66Shc in HK-2 cells exposed to HG was also observed. HK-2 cells were divided into 3 groups of 5 mmol/L glucose, 30 mmol/L glucose and 30 mmol/L glucose + 1.0 µmol/L Rottlerin. Cell immunofluorescence and Western blotting were used to observe the phosphorylation and mitochondrial translocation of p66Shc. Both mRNA expression and phosphorylation level of p66shc and PKCδ significantly increased in HK-2 cells after exposure to HG (15, 30, 45 mmol/L). And it was in a concentration- and time-dependent manner as compared with control group (up-regulated 0.9, 1.3 and 1.6-fold in mRNA of PKCδ, 0.4, 1.5 and 2.0-fold in protein of p-PKCδ respectively (all P < 0.05). PKCδ inhibitor Rottlerin dramatically inhibited the phosphorylation and mitochondrial translocation of p66Shc induced by HG in HK-2 cells (down-regulated 3.1 folds in protein of p-p66Shc in mitochondria, P < 0.01). HG increases the transcription and phosphorylation of PKCδ and p66Shc in HK-2 cells. And PKCδ may modulate the phosphorylation and mitochondrial translocation of p66Shc under.
    Zhonghua yi xue za zhi 11/2013; 93(44):3542-6.
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    ABSTRACT: Abstract Accumulation of oxidative stress is considered to be a causative mediator of kidney disease, and oxidative stress can affect some key regulators of kidney homeostasis and control a number of signaling pathways that are relevant to kidney disease. The p66Shc adaptor protein was discovered more than two decades ago as a pivotal regulator of oxidative stress. Given the importance of oxidative stress in kidney homeostasis, several molecular and cellular studies using a p66Shc antagonist have depicted a role for p66Shc in renal pathophysiology. The specificity of p66Shc functions may depend upon their intracellular localization and expression in the kidney. This review focuses on the biochemical functions of the p66Shc adaptor protein, as well as its potential implications in the pathophysiology of kidney disease. In addition, the concept that pharmacologic modulation of p66Shc expression and activity may serve as a novel and effective target for the treatment of kidney disease is discussed.
    Renal Failure 11/2013; · 0.94 Impact Factor
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    ABSTRACT: Objective: To investigate the mechanism of mitochondrial oxidative injury induced by high glucose peritoneal dialysis solution (PDS) and the protective effect of peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1α) in the mitochondria of human peritoneal mesothelial cells (HPMC) in the high glucose ambience. Methods: HPMC was cultured in a PDS containing 1.5%, 2.5% and 4.25% glucose for 24 hours. Western blot analysis was used to detect PGC-1α expression. MitoSOX? Red staining, respiratory chain complexes and antioxidant enzyme activities were determined. Results: The activities of respiratory chain complex III and antioxidant enzymes decreased significantly in a concentration- and time-dependent manner, along with the increased production of mitochondrial reactive oxygen species (ROS) and cellular apoptosis. In addition, protein expression of PGC-1α was also decreased in the high glucose PDS ambience. Conclusion: High glucose PDS might inhibit PGC-1α expression, resulting in the inhibition of mitochondrial function and increase of mitochondrial ROS and cellular apoptosis.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 11/2013; 38(11):1085-1091.
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    ABSTRACT: The aim of this study was to detect the expression of microRNA-200c and epithelial-mesenchymal transition (EMT) in the mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis (PD) patients, and to investigate the association between microRNA-200c and peritoneal mesothelial cell EMT. Twelve patients who had recently started continuous ambulatory peritoneal dialysis (PD start group) and 16 patients who had been undergoing peritoneal dialysis for >6 months (PD >6 months group) were randomly chosen for the isolation, culture and identification of effluent cells. qPCR and western blot analysis were used to detect the expression levels of microRNA-200c and the levels of four cellular marker proteins, E-cadherin, vimentin, fibronectin (FN) and COL-1, in effluent cells. The results showed that the effluent cells in peritoneal dialysis were peritoneal mesothelial cells. The level of E-cadherin protein expression was significantly lower in the PD >6 months group than in the PD start group, while vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. microRNA-200c in the PD >6 months group was significantly downregulated. The E-cadherin protein expression level was significantly decreased and vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. The level of microRNA-200c was significantly reduced in the PD > 6 months group, suggesting that microRNA-200c may be associated with EMT.
    Experimental and therapeutic medicine 11/2013; 6(5):1189-1193. · 0.34 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is thought to contribute to the progression of renal tubulointerstitial fibrosis. Norcantharidin (NCTD) is a promising agent for inhibiting renal interstitial fibrosis. However, the molecular mechanisms of NCTD are unclear. In this study, a unilateral ureteral obstruction (UUO) rat model was established and treated with intraperitoneal NCTD (0.1 mg/kg/day). The UUO rats treated with NCTD showed a reduction in obstruction-induced upregulation of α-SMA and downregulation of E-cadherin in the rat kidney (P<0.05). Human renal proximal tubule cell lines (HK-2) stimulated with TGF-β1 were treated with different concentrations of NCTD. HK-2 cells stimulated by TGF-β1 in vitro led to downregulation of E-cadherin and increased de novo expression of α-SMA; co-treatment with NCTD attenuated all of these changes (P<0.05). NCTD reduced TGF-β1-induced expression and phosphorylation of Smad2/3 and downregulated the expression of Snail1 (P<0.05). These results suggest that NCTD antagonizes tubular EMT by inhibiting the Smad pathway. NCTD may play a critical role in preserving the normal epithelial phenotype and modulating tubular EMT.
    PLoS ONE 10/2013; 8(6):e66356. · 3.53 Impact Factor

Publication Stats

592 Citations
245.15 Total Impact Points

Institutions

  • 2010–2014
    • The Second Xiangya Hospital of Central South University
      Ch’ang-sha-shih, Hunan, China
  • 2002–2014
    • Northwestern University
      • • Division of Hospital Medicine
      • • Department of Pathology
      Evanston, Illinois, United States
  • 2012
    • Peking University People's Hospital
      Peping, Beijing, China
  • 2010–2012
    • Peking University Third Hospital
      Peping, Beijing, China
  • 2006–2012
    • Sun Yat-Sen University
      • • Department of Rheumatology
      • • The First Affiliated Hospital
      Guangzhou, Guangdong Sheng, China
  • 2009–2010
    • Central South University
      • Department of Nephrology
      Changsha, Hunan, China
  • 2006–2008
    • University of Illinois at Chicago
      Chicago, Illinois, United States