scholarly journals Wenyang Lishui Decoction Ameliorates Podocyte Injury in Membranous Nephropathy Rat and Cell Models by Regulating p53 and Bcl-2

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Lu ◽  
Yuezhong Luo ◽  
Baolin Su ◽  
Shuifu Tang ◽  
Gangyi Chen ◽  
...  
Keyword(s):  
Kidney Function ◽  
Aqueous Extract ◽  
Membranous Nephropathy ◽  
Molecular Mechanisms ◽  
Distilled Water ◽  
Cell Models ◽  
Clinical Trial Registry ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor ◽  
Significant Difference

Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study in vitro showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. MN rat models were induced by cationic bovine serum albumin. Experimental rats were divided into four groups: normal, model, WYD, and benazepril. The normal group consisted of normal rats receiving distilled water for four weeks, while the model, WYD, and benazepril groups consisted of MN rats receiving distilled water, 16.5 g/kg/day WYD aqueous extract, and 10 mg/kg/day benazepril, respectively. Alanine aminotransferase, kidney function, albumin, and 24 h urine total protein (UTP) were measured. Hematoxylin-eosin and electron microscopy analyses were performed. Mouse podocytes were induced to develop cell models by serum from IMN patients with antibody to the M-type phospholipase A2 receptor and spleen and kidney Yang deficiency syndrome. They were divided into five groups: control, model, 2 mg/ml WYD, 4 mg/ml WYD, and 8 mg/ml WYD. CCK-8 assays, flow cytometry, qRT-PCR, and Western blot analyses were performed. In the animal experiment, side effects of WYD were not found. Also, there was no significant difference in kidney function among the groups. In addition, UTP level was significantly reduced, and kidney histological damage was restored in both WYD and benazepril groups but difference in UTP level between them was not found. In the cell experiment, apoptosis rate was increased in the model group while it was decreased by coincubation with WYD. Besides, mRNA and protein levels of p53 were decreased, and those of Bcl-2 were increased by treatment using WYD. In conclusion, WYD could reduce proteinuria and ameliorate podocyte injury by regulating the expression of p53 and Bcl-2. The study is registered in the Chinese Clinical Trial Registry (ChiCTR-OCH-14005137).

A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients

2020 ◽  
Vol 97 (5) ◽  
pp. 913-919 ◽  
Author(s):  
Catherine Meyer-Schwesinger ◽  
Nicola M. Tomas ◽  
Silke Dehde ◽  
Larissa Seifert ◽  
Irm Hermans-Borgmeyer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor

scholarly journals Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Dan Dong ◽  
Ting-ting Fan ◽  
Ying-ying Wang ◽  
Lu Zhang ◽  
Li Song ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Remission Rate ◽  
Meta Analysis ◽  
Negative Group ◽  
Urine Protein ◽  
Positive Group ◽  
Phospholipase A2 Receptor ◽  
Significant Difference

Abstract Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN). Methods A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis. Results Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (− 12.09, − 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate. Conclusion As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

scholarly journals Behavioral and Hematological Response of Clarias gariepinus juvenile exposed to Acute concentrations of Aqueous Extract of Siam Weed (Chloromolaena odorata) leaf as Anesthetic agent

2017 ◽  
Author(s):  
Iheanacho Stanley Chidi ◽  
Nworu Shedrack
Keyword(s):  
Aqueous Extract ◽  
Exposure Time ◽  
Hematological Parameters ◽  
Clarias Gariepinus ◽  
Blood Parameters ◽  
Anesthetic Agent ◽  
Distilled Water ◽  
Chromolaena Odorata ◽  
Blood Samples ◽  
Significant Difference

AbstractThis experiment was carried out to investigate the effect of Siam Weed (chloromelena odorata) on the heamatology of Clarias gariepinus juvenile. A total of one hundred and fifty (150) juvenile of Clarias gariepinus were randomly assigned to different concentrations of C. odorata leave aqueous extract in a completely randomize design (CRD). The concentrations were 50mg/l, 100mg/l, 150mg/l, 200mg/l. Distilled water (0.00 mg/l) was used as the control. The fish exhibited stressful behavior which was higher as the concentration of Chromolaena odorata leave extract increased. There was a gradual decrease with time until a state of calmness, which was subsequently followed by death. The effect on 96hr exposed period was recorded and blood samples collected at 24hr and 96hr interval. Result on hematological parameters revealed significant difference (P<0.05) among treatments with increase in exposure time for all the blood parameters. C. odorata at increased concentrations affected the behavior and hematology of C. gariepinus.

scholarly journals How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiffany N. Caza ◽  
Laith F. Al-Rabadi ◽  
Laurence H. Beck
Keyword(s):  
Membranous Nephropathy ◽  
Rapid Identification ◽  
Target Antigen ◽  
The Novel ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor ◽  
Major Target ◽  
Immune Complex Formation

The identification of the major target antigen phospholipase A2 receptor (PLA2R) in the majority of primary (idiopathic) cases of membranous nephropathy (MN) has been followed by the rapid identification of numerous minor antigens that appear to define phenotypically distinct forms of disease. This article serves to review all the known antigens that have been shown to localize to subepithelial deposits in MN, as well as the distinctive characteristics associated with each subtype of MN. We will also shed light on the novel proteomic approaches that have allowed identification of the most recent antigens. The paradigm of an antigen normally expressed on the podocyte cell surface leading to in-situ immune complex formation, complement activation, and subsequent podocyte injury will be discussed and challenged in light of the current repertoire of multiple MN antigens. Since disease phenotypes associated with each individual target antigens can often blur the distinction between primary and secondary disease, we encourage the use of antigen-based classification of membranous nephropathy.

scholarly journals Exploring the Differences in Molecular Mechanisms and Key Biomarkers Between Membranous Nephropathy and Lupus Nephritis Using Integrated Bioinformatics Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhaocheng Dong ◽  
Haoran Dai ◽  
Wenbin Liu ◽  
Hanxue Jiang ◽  
Zhendong Feng ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Expression Level ◽  
Renal Tubules ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Significant Difference

Background: Both membranous nephropathy (MN) and lupus nephritis (LN) are autoimmune kidney disease. In recent years, with the deepening of research, some similarities have been found in the pathogenesis of these two diseases. However, the mechanism of their interrelationship is not clear. The purpose of this study was to investigate the differences in molecular mechanisms and key biomarkers between MN and LN.Method: The expression profiles of GSE99325, GSE99339, GSE104948 and GSE104954 were downloaded from GEO database, and the differentially expressed genes (DEGs) of MN and LN samples were obtained. We used Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analysis of DEGs. A protein-protein interaction (PPI) network of DEGs was constructed using Metascape. We filtered DEGs with NetworkAnalyst. Finally, we used receiver operating characteristic (ROC) analysis to identify the most significant DEGs for MN and LN.Result: Compared with LN in the glomerulus, 14 DEGs were up-regulated and 77 DEGs were down-regulated in MN. Compared with LN in renal tubules, 21 DEGs were down-regulated, but no up-regulated genes were found in MN. According to the result of GO and KEGG enrichment, PPI network and Networkanalyst, we screened out six genes (IFI6, MX1, XAF1, HERC6, IFI44L, IFI44). Interestingly, among PLA2R, THSD7A and NELL1, which are the target antigens of podocyte in MN, the expression level of NELL1 in MN glomerulus is significantly higher than that of LN, while there is no significant difference in the expression level of PLA2R and THSD7A.Conclusion: Our study provides new insights into the pathogenesis of MN and LN by analyzing the differences in gene expression levels between MN and LN kidney samples, and is expected to be used to prepare an animal model of MN that is more similar to human.

scholarly journals The role of serum levels of anti-phospholipase A2 receptor antibodies in the diagnosis of primary membranous nephropathy.

Folia Medica ◽  
2021 ◽  
Vol 63 (5) ◽  
pp. 692-696
Author(s):  
Yovko Ronchev ◽  
Dora Terzieva ◽  
Eduard Tilkiyan
Keyword(s):  
Serum Concentration ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Disease Process ◽  
Serum Levels ◽  
Healthy Controls ◽  
Phospholipase A2 Receptor ◽  
Significant Difference ◽  
Patient Groups ◽  
Circulating Autoantibodies

Introduction: Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome in adults. The disease process is probably initiated by the binding of circulating autoantibodies to target podocyte antigens. In 2009, Beck et al. found that phospholipase A2 receptor (PLA2R1) was expressed on human podocytes in patients with PMN. Recent evidence suggests that PLA2R1 autoantibodies play an important role in the diagnosis of PMN. Aim: The aim of the present study was to compare the serum levels of anti-PLA2R1 in patients with PMN, second MN (SMN), other nephropathies (ON), and healthy controls (HC). Materials and methods: The study included 52 patients with PMN, 12 patients with SMN, 49 patients with ON, and 50 healthy controls. The serum concentration of anti-PLA2R1 was determined with ELISA kit (Anti-PLA2R ELISA, IgG, EUROIMMUN, L&uuml;beck, Germany) using MR-96A microplate Reader (MINDRAY). Statistical analysis was performed with SPSS v.22.0. Results: There was significant difference in the serum anti-PLA2R1 concentrations between patient groups and HC (p<0.0001). Compared to HC, the median anti-PLA2R1 level in the PMN group was significantly higher (4.8 RU/ml vs. 34.9 RU/ml, p=0.001), in the ON group it was lower (2.1 RU/ml, p=0.002) and did not differ in patients with SMN (2.9 RU/ml, p=0.193). The anti-PLA2R1 serum levels were significantly higher in the PMN group than in the SMN (p=0.015) and ON (p<0.001) groups. Conclusions: Our results showed that anti-PLA2R1 is significantly increased in patients with PMN. We can conclude that the anti-PLA2R1 serum concentration may be used as a beneficial biomarker for distinguishing PMN from other membranous nephropathies.

scholarly journals Perspectives in membranous nephropathy

2021 ◽  
Author(s):  
Nicola M. Tomas ◽  
Tobias B. Huber ◽  
Elion Hoxha
Keyword(s):  
Membranous Nephropathy ◽  
Treatment Strategies ◽  
Diagnosis And Treatment ◽  
Clinical Use ◽  
Podocyte Injury ◽  
Open Questions ◽  
Phospholipase A2 Receptor ◽  
Future Treatments ◽  
Made In

AbstractThe identification of the phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) as podocyte antigens in adult patients with membranous nephropathy (MN) has strongly impacted both experimental and clinical research on this disease. Evidence has been furnished that podocyte-directed autoantibodies can cause MN, and novel PLA2R- and THSD7A-specific animal models have been developed. Today, measurement of serum autoantibody levels and staining of kidney biopsies for the target antigens guides MN diagnosis and treatment worldwide. Additionally, anti-PLA2R antibodies have been proven to be valuable prognostic biomarkers in MN. Despite these impressive advances, a variety of questions regarding the disease pathomechanisms, clinical use of antibody measurement, and future treatments remain unanswered. In this review, we will outline recent advances made in the field of MN and discuss open questions and perspectives with a focus on novel antigen identification, mechanisms of podocyte injury, clinical use of antibody measurement to guide diagnosis and treatment, and the potential of innovative, pathogenesis-based treatment strategies.

Serum Anti-PLA2R Antibody Predicts Treatment Outcome in Idiopathic Membranous Nephropathy

2016 ◽  
Vol 43 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Shi-Yao Wei ◽  
Yu-Xiao Wang ◽  
Jian-Si Li ◽  
Shi-Lei Zhao ◽  
Tian-Tian Diao ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Membranous Nephropathy ◽  
Immunosuppressive Agents ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Phospholipase A2 Receptor ◽  
Significant Difference ◽  
Major Target

Background: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA2R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA2R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA2R and sPLA2R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA2R or sPLA2R-Ab positive. The sPLA2R-Ab titre, not gPLA2R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA2R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA2R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA2R intensity and outcome. Conclusions: These data indicate that sPLA2R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA2R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.

scholarly journals Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

2020 ◽  
Vol 45 (5) ◽  
pp. 713-726
Author(s):  
Ying Zhang ◽  
Yipeng Liu ◽  
Liming Liang ◽  
Liyan Liu ◽  
Xueqing Tang ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Cox Proportional Hazards ◽  
Mannose Binding Lectin ◽  
Clinical Event ◽  
Idiopathic Membranous Nephropathy ◽  
Antibody Concentration ◽  
Phospholipase A2 Receptor ◽  
Significant Difference ◽  
Mannose Binding ◽  
Binding Lectin

Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

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