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Zhou Y.,Sun Yat Sen University | Zhou Y.,Key Laboratory of Nephrology | Zhou Y.,Guangdong Provincial Key Laboratory of Nephrology | Cao S.,Sun Yat Sen University | And 22 more authors.
American Journal of Pathology | Year: 2016

Heat shock protein 72 (HSP72) has been shown to attenuate unilateral ureteral obstruction-induced kidney fibrosis. It remains unknown whether HSP72 has direct effects on fibroblast proliferation in the renal fibrotic evolution. Herein, we first confirmed that increased HSP72 expression occurred in fibrotic human kidneys. Using three different animal models of kidney fibrosis, pharmacological down-regulation or genetic deletion of endogenous HSP72 expression exacerbated STAT3 phosphorylation, fibroblast proliferation, and tubulointerstitial fibrosis. In contrast, treatment with geranylgeranyl acetone, a specific inducer of HSP72, reduced phosphorylated STAT3 and protected animals from kidney fibrosis. In cultured renal interstitial fibroblasts, overexpression of HSP72 blocked transforming growth factor (TGF)-β1-induced cell activation and proliferation, as evidenced by inhibiting expression of α-smooth muscle actin, fibronectin, and collagen I/III, as well as by reducing cell numbers and DNA synthesis. Mechanical studies showed that overexpressed HSP72 attenuated TGF-β-induced phosphorylation and nuclear translocation of STAT3 and its downstream protein expression. However, siRNA knockdown of HSP72 increased TGF-β-induced STAT3 activity and fibroblast proliferation. Ectopic expression of a constitutively active STAT3 conferred resistance to HSP72 inhibition of fibroblast proliferation. Thus, HSP72 blocks fibroblast activation and proliferation in renal fibrosis via targeting the STAT3 pathway and may serve as a novel therapeutic agent for chronic kidney disease regardless of the etiology. © 2016 American Society for Investigative Pathology.

Liao R.,Sun Yat Sen University | Liao R.,Guangdong Provincial Key Laboratory of Nephrology | Liao R.,Key Laboratory of Nephrology | Liu Q.,Sun Yat Sen University | And 25 more authors.
PLoS ONE | Year: 2015

Objective: Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function. Methods: MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2μm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-β1 for 48h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy. Results: Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-β1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF- β1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3. Conclusion: This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis. © 2015 Liao et al.

Ye H.,Sun Yat Sen University | Ye H.,Key Laboratory of Nephrology | Ye H.,Guangdong Provincial Key Laboratory of Nephrology | Chen W.,Sun Yat Sen University | And 26 more authors.
International Urology and Nephrology | Year: 2014

Objectives: The study was to investigate the prevalence and associated factors of erectile dysfunction (ED) in peritoneal dialysis (PD) patients.Methods: This was a cross-sectional survey. Eligible patients were interviewed by questionnaire: the five-item version of International Index of Erectile Function. Residual renal function (RRF) was assessed by daily urine volume and residual glomerular filtration rate.Results: Totally, 176 male prevalent PD patients were interviewed, six of them were not included in analysis for sexually inactive unrelated to ED. The prevalence of ED was 80.6 %. After adjusting for confounding factors, advance age (P = 0.014), less daily urine volume (P = 0.032) and higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.043) were independent risk factors for the development of ED.Conclusion: The prevalence of ED was high in Chinese PD patients. Advanced age, poor RRF and higher hs-CRP were independently associated with the prevalence of ED. © 2014, Springer Science+Business Media Dordrecht.

Liu Y.,Sun Yat Sen University | Liu Y.,Key Laboratory of Nephrology | Liu Y.,Guangdong Provincial Key Laboratory of Nephrology | Huang R.,Sun Yat Sen University | And 20 more authors.
British Journal of Nutrition | Year: 2015

The aim of the present study was to investigate the relationship between baseline peritoneal transport types and nutritional status in Chinese continuous ambulatory peritoneal dialysis (CAPD) patients. In the present single-centre, prospective study, incident CAPD patients were included from 15 April 2010 to 31 December 2011 and were followed up for 12 months. According to the results of baseline peritoneal equilibration test, patients were divided into lower peritoneal transport group (lower transporters) and higher peritoneal transport group (higher transporters). Nutritional status was evaluated by both subjective global assessment (SGA) and protein-energy wasting (PEW) score. The body composition parameters were assessed by body impedance analysis. A total of 283 CAPD patients were included in the study, of which 171 (60·4 %) were males with a mean age of 47·0 (sd 14·9) years. Compared with lower transporters (n 92), higher transporters (n 181) had lower levels of serum albumin (37·1 (sd 4·3) v. 39·6 (sd 4·3) g/l, P< 0·001), serum pre-albumin (356 (sd 99) v. 384 (sd 90) mg/l, P= 0·035), phase angle (6·15 (sd 0·39) v. 6·27 (sd 0·47)°, P< 0·05) and higher rate of malnutrition defined by SGA (52·5 v. 25·0 %, P< 0·001) and PEW score (37·0 v. 14·1 %, P< 0·001) at 1-year of follow-up. Baseline higher peritoneal transport, analysed by multivariate binary logistic regressions, was independently associated with malnutrition (SGA mild to moderate and severe malnutrition: OR 3·43, 95 % CI 1·69, 6·96, P< 0·01; PEW: OR 2·40, 95 % CI 1·08, 5·31, P= 0·03). It was concluded that baseline higher peritoneal transport was independently associated with worse nutritional status of CAPD patients in Southern China. © The Authors 2015.

Huang R.,Sun Yat Sen University | Huang R.,Key Laboratory of Nephrology | Huang R.,Guangdong Provincial Key Laboratory of Nephrology | Liu Y.,Sun Yat Sen University | And 23 more authors.
British Journal of Nutrition | Year: 2015

Protein-energy wasting (PEW) is strongly associated with high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. However, its clinical assessment has not been well defined. The aim of the present study was to investigate the relationship between combined nutritional indicators and mortality in CAPD patients. In the present retrospective cohort study, a total of 885 incident CAPD patients were enrolled. Nutritional status at the initiation of CAPD was assessed by BMI and biochemical indices (serum albumin, prealbumin, transferrin, creatinine and total cholesterol). The primary outcome was all-cause mortality. Principal components factor analysis was used to identify the combined nutritional parameters. Their association with mortality was examined by multivariable-adjusted Cox models. The mean age was 47·4 (sd 14·8) years, 59·2 % (n 524) were male and 24·6 % (n 218) were diabetic. Of the total patients, 130 (14·7 %) had BMI < 18·5 kg/m2, 439 (49·6 %) had albumin < 38 g/l ( < 3·8 g/dl), 303 (34·2 %) had prealbumin < 300 mg/l ( < 30 mg/dl), 404 (45·6 %) had transferrin < 2 g/l ( < 200 mg/dl), 501 (56·6 %) had total cholesterol < 5·2 mmol/l ( < 200 mg/dl) and 466 (52·7 %) had creatinine < 707 μmol/l ( < 8 mg/dl). Overall, three components such as visceral proteins, muscle-mass surrogate and BMI were extracted, which explained 69·95 % of the total variance of the nutritional parameters. After adjusting for demographic variables, co-morbid conditions, Hb, TAG and high-sensitivity C-reactive protein, the factor score of visceral proteins including albumin, prealbumin and transferrin was independently associated with mortality (hazard ratio 0·73, 95 % CI 0·60, 0·89; P= 0·002). Lower visceral protein concentrations may be independently associated with higher mortality in incident CAPD patients. Simultaneous measurements of serum albumin, prealbumin and transferrin could be helpful to monitor PEW. © The Authors 2015.

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