Drugs targeting dynamin can restore cytoskeleton and focal contact alterations of urinary podocytes derived from patients with nephrotic syndrome

Müller-Deile, Janina; Teng, Beina; Schenk, Heiko; Haller, Hermann; Reiser, Jochen; Sever, Sanja; Schiffer, Mario

doi:10.21037/atm.2016.10.72

Cited by 6 publications

(4 citation statements)

References 22 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The proposed interactions of mitf and inf2 – in particular when either protein expression is altered – could be of great relevance in understanding the dysregulation of the actin cytoskeleton induced, for example, via PAN treatment. Stabilizing components of the actin cytoskeleton can be of great therapeutic potential, as it was previously shown by our group in other animal models and human podocytes (Schiffer et al, 2015; Müller-Deile and Schiffer, 2016; Müller-Deile et al, 2016a).…”

Section: Discussionsupporting

confidence: 55%

Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy

et al. 2019

Self Cite

View full text Add to dashboard Cite

Different glomerular diseases that affect podocyte homeostasis can clinically present as nephrotic syndrome with massive proteinuria, hypoalbuminemia, hyperlipidemia and edema. Up to now, no drugs that specifically target the actin cytoskeleton of podocytes are on the market and model systems for library screenings to develop anti-proteinuric drugs are of high interest. We developed a standardized proteinuria model in zebrafish using puromycin aminonucleoside (PAN) via treatment in the fish water to allow for further drug testing to develop anti-proteinuric drugs for the treatment of glomerular diseases. We noticed that fish that carry the nacre-mutation show a significantly higher susceptibility for the disruption of the glomerular filtration barrier following PAN treatment, which results in a more pronounced proteinuria phenotype. Nacre zebrafish inherit a mutation yielding a truncated version of microphthalmia-associated transcription factor/melanogenesis associated transcription factor (mitf). We hypothesized that the nacre mutation may lead to reduced formin expression and defects in cytoskeletal rearrangement. Based on the observations in zebrafish, we carried out a PAN treatment on cultured human podocytes after knockdown with MITF siRNA causing a rearrangement of the actin cytoskeleton.

show abstract

Section: Discussionsupporting

confidence: 55%

Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Detection of podocyturia was performed as previously described by our group . Spot urine samples were centrifuged at 1200 rpm for 8 min, the supernatant was removed and the pellet was suspended in a sterile HDF solution (137 mM NaCl, 5 mM KCl, 5.5 mM glucose, 4 mM NaHCO, and 0.2% EDTA).…”

Section: Methodsmentioning

confidence: 99%

“…Detection of podocyturia was performed as previously described by our group. 31 Spot urine samples were centrifuged at 1200 rpm for 8 min, the supernatant was removed and the pellet was suspended in a sterile HDF solution (137 mM NaCl, 5 mM KCl, 5.5 mM glucose, 4 mM NaHCO, and 0.2% EDTA). The pellet was re-suspended in DMEM/F-12 medium containing 10% FCS, 0.5 U/L penicillin, and 0.5 mg/dL streptomycin after additional centrifugation at 1200 rpm for 8 minutes.…”

Section: Podocyturiamentioning

confidence: 99%

Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb

Schenk

Müller-Deile

Schmitt

et al. 2017

J of Clinical Apheresis

Self Cite

View full text Add to dashboard Cite

Treatment of primary focal segmental glomerulosclerosis (FSGS) and its recurrence after kidney transplantation associated with rapid deterioration of kidney function remains to be challenging despite advances in immunosuppressive therapy. The presence of circulating factors has been postulated to be a pivotal player in the pathogenesis of FSGS, although suPAR and CLCF-1 have been identified as the most promising causative factors. The potential therapeutic effect of suPAR elimination in an FSGS patient using CytoSorb, a hemoadsorption device that gained attention in the cytokine elimination in septic patients, was studied. Efficiency of total plasma exchange to remove suPAR was determined. CytoSorb hemoadsorption caused a 27.33% reduction of the suPAR level in a single treatment, whereas total plasma exchange showed a suPAR level reduction of 25.12% (n = 3; 95% confidence interval, 0.2777-0.8090; P < 0.01), which may indicate therapeutic potential in the treatment of primary FSGS and its recurrence in a kidney transplant.

show abstract

“…Ono and colleagues recently found that Bis-T-23 prevented proteinuria and podocyte injury in a podocyte-specific O-linked β-N-acetylglucosamine transferase knockout model (Podo-Ogt y/− ) by the same mechanism [ 197 ]. An ex vivo treatment of podocytes that detached from the GBM in two patients with FSGS and MN, respectively, was responsive to Bis-T-23, accompanied by restored cytoskeleton and focal adhesion [ 198 ]. These findings implicate the feasibility of modulating dynamin-dependent actin dynamics as a potential therapeutic approach for podocytopathies.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Cytoskeleton Rearrangement in Podocytopathies: An Update

Ma,

Qiu,

Zhang

2024

IJMS

View full text Add to dashboard Cite

Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus’s key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton.

show abstract

Drugs targeting dynamin can restore cytoskeleton and focal contact alterations of urinary podocytes derived from patients with nephrotic syndrome

Cited by 6 publications

References 22 publications

Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy

Mutation of microphthalmia-associated transcription factor (mitf) in zebrafish sensitizes for glomerulopathy

Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb

Cytoskeleton Rearrangement in Podocytopathies: An Update

Contact Info

Product

Resources

About