Translocation of dendrin to the podocyte nucleus in acute glomerular injury in patients with IgA nephropathy

Kodama, Fumiko; Asanuma, Katsuhiko; Takagi, Miyuki; Hidaka, Teruo; Asanuma, Etsuko; Fukuda, Hiromitsu; Seki, Takuto; Takeda, Yuichiro; Hosoe-Nagai, Yoshiko; Asao, Rin; Horikoshi, Satoshi; Tomino, Yasuhiko

doi:10.1093/ndt/gfs500

Cited by 24 publications

(30 citation statements)

References 45 publications

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“…The IF studies were executed as described previously [20]. After incubation, PTECs on the cover glass of the 12-well culture plates were washed three times with 100 μL of phosphate-buffered saline (PBS) at a pH of 7.4.…”

Section: Methodsmentioning

confidence: 99%

Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage

et al. 2014

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BackgroundUrinary (U)-complement components have been detected in patients with proteinuric renal diseases, and complement activation via the alternative pathway (AP) is believed to play a role in renal tubular damage. The present study aimed to examine the regulation of complement AP activation in patients with renal tubular damage by focusing on the balance between properdin (P) and factor H (fH).MethodsIn the in vivo studies, U concentrations of P, fH and membrane attack complex (MAC) were measured in patients with renal diseases using an enzyme-linked immunosorbent assay (ELISA), and their relationships with the clinical data were evaluated. In the in vitro studies, human proximal tubular epithelial cells (PTECs) were incubated with normal human serum (NHS), P-depleted serum (PDS), purified P and/or fH. Changes in cell morphology and phenotype were assessed by microscopy, real-time polymerase chain reaction (PCR), immunostaining and a cell viability assay.ResultsThe U-P, fH and MAC concentrations were significantly higher in patients with renal disease than in normal controls and correlated with the U-protein and tubular damage markers. Furthermore, multivariate analysis revealed a relationship between P levels and tubular damage markers. There were no significant changes in morphology and mRNA expression in the AP components (P, fH, fB, C3, C5 and C9) after the addition of up to 25% NHS. Dose-dependent depositions of P or fH were observed after the addition of P or fH on PTECs. Depositions of P were not inhibited by fH in a mixture of a fixed concentration of P and a variable concentration of fH, and vice versa. Preincubation with the fixed concentration of P before the addition of NHS or PDS increased the depositions of P, C3 and MAC compared with incubation with intact NHS or intact PDS only; the depositions of C3 and MAC showed a serum-dependent trend. Preincubation with P before NHS addition significantly suppressed cell viability without causing morphological changes.ConclusionsIn the pathogenesis of renal tubular damage, P can directly bind to PTECs and may accelerate AP activation by surpassing fH regulation.

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Section: Methodsmentioning

confidence: 99%

Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage

et al. 2014

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“…reduction of the absolute number per glomerulus and increase of the glomerular surface area covered by one podocyte, are related to disease progression in patients with IgA nephropathy. Thus, podocyte injury may provide additional prognostic information in these patients [13]. …”

Section: Iga Nephropathymentioning

confidence: 99%

“…My colleagues Kodama and Asanuma et al [13] investigated the existence of nuclear dendrin and the relationship between relocation of dendrin to the podocyte nucleus and disease progression in patients with IgA nephropathy. A positive correlation was observed between acute extracapillary changes and the number of dendrin-positive nuclei per glomerulus.…”

Section: Iga Nephropathymentioning

confidence: 99%

Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data

Tomino

2014

Kidney Blood Press Res

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Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD. i 2015 S. Karger AG, Basel

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“…It has been suggested that translocation of dendrin (a protein whose function is still unclear) into the nucleus results in apoptosis and loss of podocytes [65,66]. In addition to the translocation of dendrin, downregulation of anti-apoptotic Bcl-2 in podocytes has been associated with elevated serum creatinine, a decline in creatinine clearance, and an increase in proteinuria in IgAN [67].…”

Section: Podocyte-specific Biomarkersmentioning

confidence: 99%

Biomarkers in IGA Nephropathy

et al. 2014

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IgA nephropathy is the most common primary glomerulonephritis and presents with gross hematuria and upper respiratory infection, with slow progression to end-stage renal disease in up to 50% of affected patients. Kidney biopsies are the gold standard method of diagnosis and frequently are not performed as the majority of individuals are asymptomatic. Thus, there is a need to discover and validate prognostic and predictive biomarkers that can be noninvasively obtained and are specific to this disease. Here we discuss the current state of research in this area and examine validated and clinically promising biofluid and tissue biomarkers of IgA nephropathy.

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Translocation of dendrin to the podocyte nucleus in acute glomerular injury in patients with IgA nephropathy

Cited by 24 publications

References 45 publications

Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage

Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage

Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data

Biomarkers in IGA Nephropathy

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