ABSTRACT
Long-term peritoneal dialysis (PD) leads to ultrafiltration failure (UFF). Peritoneal mesothelial cells, which form the innermost monolayer of the peritoneal cavity, have been shown to regulate various responses, including inflammation, in UFF. The present study was designed to investigate the effect of the peroxisome proliferatoractivated receptorγ (PPARγ) agonist, rosiglitazone, on peritoneal dialysis solution (PDS)induced injuries in rat peritoneal mesothelial cells (RPMCs). RPMCs were cultured for different durations and with different concentrations of PDS. The gene expression levels of aquaporin1 (AQP1) and zonula occluden1 (ZO1) were determined using reverse transcriptionquantitative polymerase chain reaction analysis. The protein levels of AQP1, ZO1 and PPARγ were measured using western blot analysis. Interleukin (IL)6 and IL8 were detected using ELISA. The RPMCs were damaged by stimulation with 4.25% PDS for 72 h. The expression levels of AQP1 and ZO1 were increased, and the secretion of IL6 and IL8 were decreased by rosiglitazone. The use of the PPARγ inhibitor, GW9662, completely prevented the effects of rosiglitazone. These results indicated that PDS exposure stimulated an inflammatory response in the RPMCs. The PPARγ activator, rosiglitazone, appeared to relieve the injury by inhibiting inflammation, and regulating the expression of AQP1 and ZO1, however further investigations are required to elucidate the potential underlying mechanism.
Subject(s)
Dialysis Solutions/adverse effects , Epithelial Cells/drug effects , PPAR gamma/agonists , Peritoneal Dialysis/adverse effects , Peritoneum/drug effects , Protective Agents/therapeutic use , Thiazolidinediones/therapeutic use , Animals , Aquaporin 1/analysis , Aquaporin 1/genetics , Epithelial Cells/pathology , Interleukin-6/analysis , Interleukin-6/metabolism , Interleukin-8/analysis , Interleukin-8/metabolism , Male , PPAR gamma/analysis , PPAR gamma/metabolism , Peritoneum/cytology , Peritoneum/pathology , RNA, Messenger/genetics , Rats, Sprague-Dawley , Rosiglitazone , Zonula Occludens-1 Protein/analysis , Zonula Occludens-1 Protein/geneticsABSTRACT
Ischemiareperfusion (I/R) injury is important in the pathogenesis and/or progression of various diseases, including stroke, cardiovascular disease and acute renal injury. Increasing evidence indicates that atorvastatin exerts protective effects in I/R injuryassociated diseases; however, the underlying mechanisms remain to be fully elucidated. In the present study, oxygenglucose deprivation (OGD)/reperfusionstimulated. RAW264.7 murine macrophages served as a model of I/R injury. The knockdown of peroxisome proliferator activated receptorγ (PPARγ) expression in these cells increased OGD/reperfusioninduced expression of inducible nitric oxide synthase (iNOS), tumor necrosis factorα (TNFα) and interferonγ (IFNγ), and enhanced OGD/reperfusioninduced downregulation of the expression of cluster of differentiation (CD) 206, at the mRNA and protein levels. Conversely, overexpression of PPARγ significantly attenuated OGD/reperfusioninduced alterations in the expression of iNOS, TNFα, IFNγ and CD206 at the mRNA and protein levels. Notably, atorvastatin inhibited OGD/reperfusioninduced iNOS expression and reversed OGD/reperfusioninduced downregulation of the expression of CD206 and PPARγ at the mRNA and protein levels. The results of the present study indicate that atorvastatin exhibits significant antiinflammatory effects in OGD/reperfusionstimulated RAW264.7 cells, possibly via PPARγ regulation. The findings of the present study may reveal a novel mechanism underlying the protective effects of atorvastatin in I/R injuryassociated diseases.
Subject(s)
Atorvastatin/administration & dosage , Inflammation/drug therapy , PPAR gamma/genetics , Reperfusion Injury/drug therapy , Animals , Disease Models, Animal , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Glucose/metabolism , Humans , Inflammation/genetics , Inflammation/pathology , Interferon-gamma/biosynthesis , Lectins, C-Type/biosynthesis , Mannose Receptor , Mannose-Binding Lectins/biosynthesis , Mice , Nitric Oxide Synthase Type II/biosynthesis , Oxygen/metabolism , PPAR gamma/antagonists & inhibitors , RAW 264.7 Cells , Receptors, Cell Surface/biosynthesis , Reperfusion Injury/genetics , Reperfusion Injury/pathology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
OBJECTIVE: To explore the relation between the frequencies of apolipoprotein E (ApoE) alleles and the occurrence of depression in patients undergoing hemodialysis in a Chinese population. METHODS: We examined the ApoE alleles in a sample of 288 subjects: 72 patients with depression under hemodialysis, 74 patients without depression under hemodialysis, 75 patients with depression under nondialytic treatment and 67 patients without depression under nondialytic treatment. The depression state was assessed using the Center for Epidemiological Studies Depression (CES-D) scale. Associations between the occurrence of depression and the frequencies of ApoE alleles were examined using multinomial logistic regression models with adjustment of relevant covariates. Information about sociodemographics, clinical data, vascular risk factors and cognitive function was also collected and evaluated. RESULTS: The frequencies of ApoE-É2 were significantly different between depressed and non-depressed patients irrespective of dialysis (p < 0.05), but no significant difference was found in the frequencies of ApoE-É4 (p > 0.05). Serum ApoE levels were significantly different between depressed and non-depressed patients in the whole sample (p < 0.05). Multinomial logistic regression models showed significant association between the frequency of ApoE-É2 and the occurrence of depression in the Chinese population after control of relevant covariates, including age, sex, educational level, history of smoking and drinking, vascular risk factors and cognitive function. CONCLUSIONS: No association between the frequency of ApoE-É4 and the occurrence of depression was found in patients undergoing hemodialysis. Further research is needed to find out if ApoE-É2 acts as a protective factor in Chinese dialysis population since it might decrease the prevalence of depression and delay the onset age.