scholarly journals An Overview of Molecular Mechanism of Nephrotic Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana Reis Machado ◽  
Laura Penna Rocha ◽  
Precil Diego Miranda de Menezes Neves ◽  
Eliângela de Castro Cobô ◽  
Marcos Vinícius Silva ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Epithelial Mesenchymal Transition ◽  
Membrane Damage ◽  
Membranous Glomerulonephritis ◽  
Basal Membrane ◽  
Experimental Models ◽  
Mesenchymal Transition ◽  
Disease Occurrence ◽  
Phospholipase A2 Receptor

Podocytopathies (minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS)) together with membranous nephropathy are the main causes of nephrotic syndrome. Some changes on the expression of nephrin, podocin, TGF-β, and slit diaphragm components as well as transcription factors and transmembrane proteins have been demonstrated in podocytopathies. Considering the pathogenesis of proteinuria, some elucidations have been directed towards the involvement of epithelial-mesenchymal transition. Moreover, the usefulness of some markers such as TGF-β1, nephrin, synaptopodin, dystroglycans, and malondialdehyde have been determined in the differentiation between MCD and FSGS. Experimental models and human samples indicated an essential role of autoantibodies in membranous glomerulonephritis, kidney damage, and proteinuria events. Megalin and phospholipase-A2-receptor have been described as antigens responsible for the formation of the subepithelial immune complexes and renal disease occurrence. In addition, the complement system seems to play a key role in basal membrane damage and in the development of proteinuria in membranous nephropathy. This paper focuses on the common molecular changes involved in the development of nephrotic proteinuria.

scholarly journals Successful foetal outcome in a patient with primary membranous nephropathy and circulating anti-phospholipid antibodies: A case report

2018 ◽  
Keyword(s):  
Nephrotic Syndrome ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Phospholipase A2 Receptor ◽  
Foetal Outcome ◽  
Circulating Autoantibodies ◽  
Patient’S History

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

Successful foetal outcome in a patient with primary membranous nephropathy and circulating anti-phospholipid antibodies: A case report

2018 ◽  
Author(s):  
Evgeny Farber
Keyword(s):  
Nephrotic Syndrome ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Phospholipase A2 Receptor ◽  
Foetal Outcome ◽  
Circulating Autoantibodies ◽  
Patient’S History

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

scholarly journals Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Chenqiang Jia ◽  
Zhuqing Zhang ◽  
Jun Tang ◽  
Mei-Chun Cai ◽  
Jingyu Zang ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcriptional Activation ◽  
Promoter Region ◽  
Drug Exposure ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Models ◽  
Cytokine Release ◽  
Functional Importance ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

scholarly journals Contactin 1: An Important and Emerging Oncogenic Protein Promoting Cancer Progression and Metastasis

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 874
Author(s):  
Yan Gu ◽  
Taosha Li ◽  
Anil Kapoor ◽  
Pierre Major ◽  
Damu Tang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
System Development ◽  
Notch Signaling Pathway ◽  
Experimental Models ◽  
Vegf Receptor ◽  
Mesenchymal Transition ◽  
Cancer Pathways ◽  
Factor C

Even with recent progress, cancer remains the second leading cause of death, outlining a need to widen the current understanding on oncogenic factors. Accumulating evidence from recent years suggest Contactin 1 (CNTN1)’s possession of multiple oncogenic activities in a variety of cancer types. CNTN1 is a cell adhesion molecule that is dysregulated in many human carcinomas and plays important roles in cancer progression and metastases. Abnormalities in CNTN1 expression associate with cancer progression and poor prognosis. Mechanistically, CNTN1 functions in various signaling pathways frequently altered in cancer, such as the vascular endothelial growth factor C (VEGFC)-VEGF receptor 3 (VEFGR3)/fms-related tyrosine kinase 4 (Flt4) axis, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), Notch signaling pathway and epithelial-mesenchymal transition (EMT) process. These oncogenic events are resulted via interactions between tumor and stroma, which can be contributed by CNTN1, an adhesion protein. CNTN1 expression in breast cancer correlates with the expression of genes functioning in cancer-stroma interactions and skeletal system development. Evidence supports that CNTN1 promotes cancer-stromal interaction, resulting in activation of a complex network required for cancer progression and metastasis (bone metastasis for breast cancer). CNTN1 inhibitions has been proven to be effective in experimental models to reduce oncogenesis. In this paper, we will review CNTN1′s alterations in cancer, its main biochemical mechanisms and interactions with its relevant cancer pathways.

Membranous glomerulonephritis

2018 ◽  
Author(s):  
Daniel C. Cattran ◽  
Heather N. Reich
Keyword(s):  
Nephrotic Syndrome ◽  
Hepatitis B ◽  
Renal Biopsy ◽  
Clinical Picture ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Hepatitis B Infection ◽  
Immunoglobulin G4 ◽  
Secondary Membranous Nephropathy ◽  
Secondary Causes

Membranous glomerulonephritis (MGN) usually presents as nephrotic syndrome, which may be severe. It is primarily a disease of adults, men more than women, with a peak incidence in the fourth and fifth decades. It is hoped that proven tests for the characteristic anti-PLA2R antibodies of primary MGN may become established, but the diagnosis currently rests on renal biopsy showing characteristic subepithelial granular immune deposits. These usually contain immunoglobulin G4 and complement. Other patterns may suggest secondary causes of MGN. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers. Secondary causes are more common at extremes of age, and are often made obvious by the history or clinical picture. How hard to look for malignancy is controversial, but malignancy is much more likely in patients over 60 years, and may be apparent at presentation.

Membranous glomerulonephritis

2018 ◽  
Author(s):  
Daniel C. Cattran ◽  
Heather N. Reich
Keyword(s):  
Membranous Nephropathy ◽  
Adult Life ◽  
Membranous Glomerulonephritis ◽  
Adult Onset ◽  
Common Cause ◽  
End Stage Renal Failure ◽  
Surface Molecules ◽  
Phospholipase A2 Receptor ◽  
Secondary Membranous Nephropathy ◽  
End Stage

Membranous glomerulonephritis (MGN) is the most common cause of adult-onset nephrotic syndrome, and a common glomerular cause of end-stage renal failure. It is caused by antibodies to podocyte surface molecules, usually autoantibodies. In most patients with primary membranous nephropathy the target is the phospholipase A2 receptor. It is hoped that robust assays for this antibody will help to guide therapy but it has not been possible to test this adequately yet. Primary MGN accounts for about 70% of cases with regional variations. MGN is more common in men than women (approximately 2:1) and its peak incidence is in middle adult life. Secondary membranous nephropathy occurs in lupus and some other immune or autoimmune disorders, in hepatitis B infection, after exposure to some drugs or toxins, and in some cancers.

scholarly journals Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice

2020 ◽  
Vol 8 ◽  
pp. 232470962096721
Author(s):  
Faisal Inayat ◽  
Talal Almas ◽  
Syed Rizwan A. Bokhari ◽  
Aun Muhammad ◽  
Moh’d A. Sharshir
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Practice ◽  
Membranous Nephropathy ◽  
Adult Population ◽  
Relevant Literature ◽  
Immunosuppressive Treatment ◽  
Membranous Glomerulonephritis ◽  
Interesting Case ◽  
Secondary Syphilis ◽  
Uncommon Presentation

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

scholarly journals RANKL Immunisation Inhibits Prostate Cancer Metastasis by Modulating EMT Through a RANKL-dependent Pathway

2020 ◽  
Author(s):  
Mineon Park ◽  
Yong Jin Cho ◽  
Bora Kim ◽  
Young Jong Ko ◽  
Yuria Jang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Models ◽  
University Hospital ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Pc3 Cells ◽  
Tissue Specimens

Abstract Background: Prostate cancer (PCa) morbidity in the majority of patients is due to metastatic events, which are a clinical obstacle. Therefore, a better understanding of the mechanism underlying metastasis is imperative if we are to develop novel therapeutic strategies. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) regulates bone remodelling. RANKL was associated with epithelial-mesenchymal transition (EMT) and expression of metastasis-related genes in PC3 cells. Thus, agents that suppress RANKL signalling may be useful pharmacological treatments. Method: In this study, we proposed a strategy to induce anti-cytokine antibodies using mutant RANKL as an immunogen. Here, we used preclinical experimental models to investigate whether an inactive form of RANKL affects bone metastasis in RANKL-induced PCa.Results: RANKL activation was observed in human PCa tissue specimens. RANKL promoted migration and invasion of PC3 cells through EMT, and induced a significant increase in binding of β-catenin to TCF-4, an EMT-induced transcription factor in PCa cells, via mitogen-activated protein kinase and β-catenin/TCF-4 signalling. Thus, RANKL increased EMT and the metastatic properties of PC3 cells, suggesting a role as a therapeutic target to prevent PCa metastasis. Conclusion: Treatment with mutant RANKL reduced EMT and metastasis of PC3 PCa cells in an experimental metastasis model. Thus, mutant RANKL could serve as a potential vaccine to prevent and treat metastatic PCaTrial registration: Chosun University Hospital, CHOSUN 2020-06-001. Registered 01 June 2020-prospectevely registered, https://hosp.chosun.ac.kr/medi_depart/?site=hospital&mn=151&type=view&catename=IRB

scholarly journals Pulmonary Embolism Revealing Idiopathic Membranous Glomerulonephritis

2010 ◽  
Vol 2010 ◽  
pp. 1-3
Author(s):  
A. Hamzaoui ◽  
O. Harzallah ◽  
R. Klii ◽  
L. Njim ◽  
S. Mahjoub
Keyword(s):  
Pulmonary Embolism ◽  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Membranous Glomerulonephritis ◽  
Idiopathic Membranous Nephropathy ◽  
Idiopathic Membranous Glomerulonephritis

We describe a case of a 55-year-old man who presented with pulmonary embolism and who was found to have nephrotic syndrome due to idiopathic membranous nephropathy. There are no other signs of nephrotic syndrome such as edema.

Sign in / Sign up

Export Citation Format

Share Document