4D <i>in vivo</i> imaging of glomerular barrier function in a zebrafish podocyte injury model

Siegerist, Florian; Zhou, Weibin; Endlich, Karlhans; Endlich, Nicole

doi:10.1111/apha.12754

Cited by 28 publications

(37 citation statements)

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“…bdnf KD larvae developed pericardial oedema as an indicator for an impairment of the glomerular filtration barrier. This finding could be confirmed by a decrease in the intravascular eGFP intensity in bdnfMO‐treated CADE larvae, also indicating a leaky filtration barrier . We also found a reduced expression of the podocyte markers podocin and nephrin, and a disrupted F‐actin structure in bdnfMO‐treated larvae, which are suggestive of podocyte loss.…”

Section: Discussionsupporting

confidence: 77%

“…Furthermore, bdnf KD larvae showed reduced expression of nphs2 (podocin) in RT‐PCR analysis (Figure C), which was confirmed by qRT‐PCR (Figure D). To study the glomerular morphology, we stained cryosections of zebrafish larvae, utilizing the ET strain that expresses eGFP specifically in podocytes . After staining the F‐actin cytoskeleton with Alexa‐546 phalloidin, we observed significant changes in the morphology of the glomeruli in response to the KD of bdnf .…”

Section: Resultsmentioning

confidence: 99%

“…To study the glomerular morphology, we stained cryosections of zebrafish larvae, utilizing the ET strain that expresses eGFP specifically in podocytes. 28,30 After staining the F-actin cytoskeleton with Alexa-546 phalloidin, we observed significant changes in the morphology of the glomeruli in response to the KD of bdnf. In addition to an enlargement of the glomerular tuft and Bowman's space, we observed a reduced number of podocytes in bdnf KD larvae (3 dpf) in contrast to CtrlMO-treated zebrafish larvae ( Figure 6A).…”

Section: Bdnf Is Important For the Proper Morphology Of Zebrafish Gmentioning

confidence: 92%

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BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Endlich

Lange

Kuhn

et al. 2018

J Cellular Molecular Medi

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Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM‐1, CTSL by qRT‐PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM‐1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM‐1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker.

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Section: Discussionsupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Bdnf Is Important For the Proper Morphology Of Zebrafish Gmentioning

confidence: 92%

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BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Endlich

Lange

Kuhn

et al. 2018

J Cellular Molecular Medi

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“…For the study of podocytes in vivo in the intact kidney, different modalities of intravital multiphoton microscopy (MPM) have emerged in the past few years [2, 5, 6, 9, 24–26, 32]. Thanks to MPM, it is now possible not only to study the three-dimensional architecture and cellular complexity of the GFB [5, 27] but also most importantly to quantitatively visualize the many dynamic functional features of glomerular filtration [2, 9], capillary blood flow [2, 9, 24, 27], albumin leakage [1, 21, 27, 30, 32], podocyte calcium [1], motility [1, 5, 27, 34], and detachment in vivo [27]. Also, the interactions between glomerular endothelial and mesangial cells and podocytes in the intact living rat and mouse kidney can be visualized with MPM in great detail [27].…”

Section: Introductionmentioning

confidence: 99%

Combined use of electron microscopy and intravital imaging captures morphological and functional features of podocyte detachment

Burford

Gyarmati

Shirato

et al. 2017

Pflugers Arch - Eur J Physiol

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The development of podocyte injury and albuminuria in various glomerular pathologies is still incompletely understood due to technical limitations in studying the glomerular filtration barrier (GFB) in real-time. We aimed to directly visualize the early morphological and functional changes of the GFB during the development of focal segmental glomerulosclerosis (FSGS) using a combination of transmission electron microscopy (TEM) and in vivo multiphoton microscopy (MPM) in the rat puromycin aminonucleoside (PAN) model. We hypothesized that this combined TEM + MPM experimental approach would provide a major technical improvement that would benefit our mechanistic understanding of podocyte detachment. Male Sprague-Dawley (for TEM) or Munich-Wistar-Frömter (for MPM) rats were given a single dose of 100–150 mg/kg body weight PAN i.p. and were either sacrificed and the kidneys processed for TEM or surgically instrumented for in vivo MPM imaging at various times 2–14 days after PAN administration. Both techniques demonstrated hypertrophy and cystic dilatations of the subpodocyte space that developed as early as 2–3 days after PAN. Adhesions of the visceral epithelium to the parietal Bowman’s capsule (synechiae) appeared at days 8–10. TEM provided unmatched resolution of podocyte foot process remodeling, while MPM revealed the rapid dynamics of pseudocyst filling, emptying, and rupture, as well as endothelial and podocyte injury, misdirected filtration, and podocyte shedding. Due to the complementary advantages of TEM and MPM, this combined approach can provide an unusally comprehensive and dynamic portrayal of the alterations in podocyte morphology and function during FSGS development. The results advance our understanding of the role and importance of the various cell types, hemodynamics, and mechanical forces in the development of glomerular pathology.

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“…Citations to articles from 2018 are weighted more than those appearing the year before, as the window for referencing these manuscripts is narrower. More than 20 articles have received double‐digit citations so far, many in the field of renal physiology . One of these renal physiology manuscripts, however, does not qualify for the prize, as one author is also an editor for the journal.…”

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confidence: 99%

Upcoming Acta Physiologica Award of US$ 100,000.00

Persson

2019

Acta Physiologica

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4D in vivo imaging of glomerular barrier function in a zebrafish podocyte injury model

Abstract: We established a microscopy-based method to monitor the dynamics of glomerular barrier function during induction of podocyte injury in multiple zebrafish larvae simultaneously over 26 h.

Cited by 28 publications

References 28 publications

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Combined use of electron microscopy and intravital imaging captures morphological and functional features of podocyte detachment

Upcoming Acta Physiologica Award of US$ 100,000.00

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