scispace - formally typeset
Search or ask a question
Author

Liping Xiong

Bio: Liping Xiong is an academic researcher from Sun Yat-sen University. The author has contributed to research in topics: Peritoneal dialysis & Continuous ambulatory peritoneal dialysis. The author has an hindex of 8, co-authored 13 publications receiving 243 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: Atg5-mediated autophagy in proximal epithelial cells is a critical host-defense mechanism that prevents renal fibrosis by blocking G2/M arrest, suggesting the regulation of cell cycle progression by ATG5 is Autophagy dependent.
Abstract: Macroautophagy/autophagy protects against cellular stress. Renal sublethal injury-triggered tubular epithelial cell cycle arrest at G2/M is associated with interstitial fibrosis. However, the role of autophagy in renal fibrosis is elusive. Here, we hypothesized that autophagy activity in tubular epithelial cells is pivotal for inhibition of cell cycle G2/M arrest and subsequent fibrogenic response. In both renal epithelial cells stimulated by angiotensin II (AGT II) and the murine kidney after unilateral ureteral obstruction (UUO), we observed that occurrence of autophagy preceded increased production of COL1 (collagen, type I). Pharmacological enhancement of autophagy by rapamycin suppressed COL1 accumulation and renal fibrosis. In contrast, genetic ablation of autophagy by proximal tubular epithelial cell-specific deletion of Atg5, with reduction of the LC3-II protein level and degradation of SQSTM1/p62, showed marked cell cycle arrest at the G2/M phase, robust COL1 deposition, and severe interstitial fibrosis in a UUO model, as compared with wild-type mice. In vitro, AGT II exposure triggered autophagy preferentially in the G1/S phase, and increased COL1 expression in the G2/M phase in renal epithelial cells. Stimulation of Atg5-deficient primary proximal tubular cells with AGT II also resulted in elevated G2/M arrest and COL1 production. Pharmacological or genetic inhibition of autophagy increased AGT II-mediated G2/M arrest. Enhanced expression of ATG5, but not the autophagy-deficient ATG5 mutant K130R, rescued the G2/M arrest, suggesting the regulation of cell cycle progression by ATG5 is autophagy dependent. In conclusion, Atg5-mediated autophagy in proximal epithelial cells is a critical host-defense mechanism that prevents renal fibrosis by blocking G2/M arrest.

134 citations

Journal ArticleDOI
TL;DR: The results imply that inhibiting p-Drp1S616-mediated mitochondrial fission attenuates fibroblast activation and proliferation in renal fibrosis through epigenetic regulation of fibrosis-related genes transcription and may serve as a therapeutic target for retarding progression of chronic kidney disease.
Abstract: Excessive mitochondrial fission acts as a pro-proliferative marker in some cancers and organ fibrosis; its potential role in renal fibroblast activation and fibrogenesis has never been investigated. Here, we showed more pronounced fragmented mitochondria in fibrotic than in non-fibrotic renal fibroblast in humans and mice. In a mouse model of obstructive nephropathy, phosphorylation of Drp1 at serine 616 (p-Drp1S616) and acetylation of H3K27(H3K27ac) was increased in fibrotic kidneys; pharmacological inhibition of mitochondrial fission by mdivi-1 substantially reduced H3K27ac levels, fibroblasts accumulation, and interstitial fibrosis. Moreover, mdivi-1 treatment was able to attenuate the established renal fibrosis. In cultured renal interstitial fibroblasts, targeting Drp1 using pharmacological inhibitor or siRNA suppressed TGF-β1-elicited cell activation and proliferation, as evidenced by inhibiting expression of α-smooth muscle actin (α-SMA) and collagen I, as well as by reducing DNA synthesis. In contrast, Drp1 deletion enhanced cell apoptosis, along with decreased mitochondrial fragmentation, mtROS elevation, and glycolytic shift upon TGF-β1 stimulation. In Drp1 deletion fibroblasts, re-expression of wild-type Drp1 rather than Drp1S616A mutant restores the reduction of TGF-β-induced-Drp1 phosphorylation, H3K27ac, and cell activation. Moreover, TGF-β1 treatment increased the enrichment of H3K27ac at the promoters of α-SMA and PCNA, which was reversed in Drp1-knockdown fibroblasts co-transfected with empty vector or Drp1S616A, but not wild-type Drp1. Collectively, our results imply that inhibiting p-Drp1S616-mediated mitochondrial fission attenuates fibroblast activation and proliferation in renal fibrosis through epigenetic regulation of fibrosis-related genes transcription and may serve as a therapeutic target for retarding progression of chronic kidney disease.

55 citations

Journal ArticleDOI
27 Jan 2014-PLOS ONE
TL;DR: A lower serum potassium level was associated with all-cause and cardiovascular mortality during the first year of follow-up in incident PD patients and higher variability of serum potassium levels conferred an increased risk of death in this population of patients.
Abstract: Background Abnormal serum potassium is associated with an increased risk of mortality in dialysis patients. However, the impacts of serum potassium levels on short- and long-term mortality and association of potassium variability with death in peritoneal dialysis (PD) patients are uncertain. Methods We examined mortality-predictability of serum potassium at baseline and its variability in PD patients treated in our center January 2006 through December 2010 with follow-up through December 2012. The hazard ratios (HRs) were used to assess the relationship between baseline potassium levels and short-term (≤1 year) as well as long-term (>1 year) survival. Variability of serum potassium was defined as the coefficient of variation of serum potassium (CVSP) during the first year of PD. Results A total of 886 incident PD patients were enrolled, with 248 patients (27.9%) presented hypokalemia (serum potassium <3.5 mEq/L). During a median follow-up of 31 months (range: 0.5–81.0 months), adjusted all-cause mortality hazard ratio (HR) and 95% confidence interval (CI) for baseline serum potassium of <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.5 to <5.0, and ≥5.0 mEq/L, compared with 4.0 to <4.5 (reference), were 1.79 (1.02–3.14), 1.15 (0.72–1.86), 1.31 (0.82–2.08), 1.33 (0.71–2.48), 1.28 (0.53–3.10), respectively. The increased risk of lower potassium with mortality was evident during the first year of follow-up, but vanished thereafter. Adjusted all-cause mortality HR for CVSP increments of 7.5% to <12.0%; 12.0% to <16.7% and ≥16.7%, compared with <7.5% (reference), were 1.35 (0.67–2.71), 2.00 (1.05–3.83) and 2.18 (1.18–4.05), respectively. Similar association was found between serum potassium levels and its variability and cardiovascular mortality. Conclusions A lower serum potassium level was associated with all-cause and cardiovascular mortality during the first year of follow-up in incident PD patients. In addition, higher variability of serum potassium levels conferred an increased risk of death in this population.

47 citations

Journal ArticleDOI
TL;DR: A higher serum TG/HDL-C ratio was associated with an increased risk of all-cause and CVD mortality in PD patients, and this association was significantly higher in female than male PD patients.
Abstract: Background and aims High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been found to be an independent predictor for cardiovascular events in the general population. We aimed to evaluate whether a high TG/HDL-C ratio was associated with an increased risk of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Methods and results In this single-center retrospective cohort study, 1170 incident patients on peritoneal dialysis (PD) from 1 January 2007 to 31 December 2011 were recruited and followed up until 31 December 31 2013. The mean age was 47.4 ± 15.2 years, and 24.7% were diabetic. During a median of the 34.5-month follow-up period, 213 (18.2%) deaths occurred, 121 of which (56.8%) were caused by cardiovascular disease (CVD). The serum median TG/HDL-C ratio at baseline was 2.57 (range: 0.06–39.39). On multivariate Cox regression analysis, the highest quartile of the TG/HDL-C ratio (≥4.19) was associated with increased risk of all-cause mortality (hazard ratio (HR) 1.98, 95% confidence interval (CI), 1.17–3.36; P = 0.011) and CVD mortality (HR 2.28, 95% CI, 1.16–4.47; P = 0.017). For female patients, each one-unit higher baseline TG/HDL-C was associated with 13% (95% CI 1.06–1.22; P = 0.001) increased risk of CVD mortality, whereas such an association was not observed for male patients, (HR 1.00, 95% CI 0.92–1.08; P = 0.977). Conclusions A higher serum TG/HDL-C ratio was associated with an increased risk of all-cause and CVD mortality in PD patients. Moreover, the increased risk of CVD mortality was significantly higher in female than male PD patients.

28 citations

Journal ArticleDOI
TL;DR: The prevalence of pulmonary hypertension at the start of peritoneal dialysis was common and associated with increased risk of both all-cause and cardiovascular mortality in incident PD patients.
Abstract: BackgroundThe prognostic value of pulmonary hypertension at the start of peritoneal dialysis (PD) in patient survival is unclear.MethodsWe conducted a retrospective study of incident patients who i...

21 citations


Cited by
More filters
Journal Article
15 Mar 1990-Harefuah
TL;DR: Patients with rapid absorption of glucose have low drain water ultrafiltration volumes but higher creatinine clearances, and therefore need adjustment of the therapy plan or else should be on hemodialysis.
Abstract: 7 men and 3 women (mean age 62 +/- 11 years) with end-stage renal disease, who were on continuous ambulatory peritoneal dialysis, underwent a peritoneal equilibration test to determine the rate of peritoneal ultrafiltration and creatinine transfer. The test is based on glucose absorption into the plasma from the peritoneal solution and the diffusion of creatinine into the peritoneal fluid after 2-4 hours. Patients with rapid absorption of glucose have low drain water ultrafiltration volumes but higher creatinine clearances, and therefore need adjustment of the therapy plan or else should be on hemodialysis. No correlation was found between the time the patients were on treatment and glucose absorption or creatinine diffusion.

411 citations

Journal ArticleDOI
TL;DR: The authors review drivers of fibrogenesis, including epithelial cell injury, inflammation, regeneration pathways and factors that promote the AKI-to-CKD transition, and discuss direct targeting of fibrotic pathways and therapeutic approaches that have reportedly decreased kidney fibrosis in preclinical and/or clinical studies.
Abstract: Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells. Here, the authors review drivers of fibrogenesis, including epithelial cell injury, inflammation, regeneration pathways and factors that promote the AKI-to-CKD transition. They discuss direct targeting of fibrotic pathways and therapeutic approaches that have reportedly decreased kidney fibrosis in preclinical and/or clinical studies.

341 citations

Journal ArticleDOI
TL;DR: CKD is associated with significant changes in cell signaling in kidney tissues, including the activation of transforming growth factor-β, p53, hypoxia-inducible factor, and major developmental pathways, which may contribute to the heightened sensitivity of, and nonrecovery from, AKI.

237 citations

Journal ArticleDOI
TL;DR: Conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas are provided.

225 citations

Journal ArticleDOI
TL;DR: The authors summarize the basics of autophagy and the signalling pathways involved in its regulation, and examine the multiple roles of autophile in kidney cells, from its involvement in kidney maintenance and responses to injury, to its potential contribution to glomerular and tubulointerstitial disease.
Abstract: Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic components. Basal autophagy in kidney cells is essential for the maintenance of kidney homeostasis, structure and function. Under stress conditions, autophagy is altered as part of the adaptive response of kidney cells, in a process that is tightly regulated by signalling pathways that can modulate the cellular autophagic flux — mammalian target of rapamycin, AMP-activated protein kinase and sirtuins are key regulators of autophagy. Dysregulated autophagy contributes to the pathogenesis of acute kidney injury, to incomplete kidney repair after acute kidney injury and to chronic kidney disease of varied aetiologies, including diabetic kidney disease, focal segmental glomerulosclerosis and polycystic kidney disease. Autophagy also has a role in kidney ageing. However, questions remain about whether autophagy has a protective or a pathological role in kidney fibrosis, and about the precise mechanisms and signalling pathways underlying the autophagy response in different types of kidney cells and across the spectrum of kidney diseases. Further research is needed to gain insights into the regulation of autophagy in the kidneys and to enable the discovery of pathway-specific and kidney-selective therapies for kidney diseases and anti-ageing strategies. In this Review, the authors summarize the basics of autophagy and the signalling pathways involved in its regulation, and examine the multiple roles of autophagy in kidney cells, from its involvement in kidney maintenance and responses to injury, to its potential contribution to glomerular and tubulointerstitial disease.

192 citations