Assessment of detached podocytes in the Bowman's space as a marker of disease activity in lupus nephritis

Moustafa, Fatma; Soliman, Nahed A.; Bakr, Ashraf; Shwaf, I M El

doi:10.1177/0961203313514125

Cited by 9 publications

(6 citation statements)

References 7 publications

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“…More recently, several groups have shown that podocytes themselves do migrate to Bowman's capsule following podocyte depletion (9,14,26,27,40,41) mice in the current study to determine whether this phenomenon exists. As expected, at baseline before disease in mice that received doxycycline to induce permanent podocyte labeling, ZsGreen fluorescence was restricted to podocytes in the glomerular tuft, and was not detected along Bowman's capsule.…”

Section: A B Cmentioning

confidence: 81%

Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources

Kaverina

Eng

Schneider

et al. 2016

American Journal of Physiology-Renal Physiology

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The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the podocyte markers p57, synaptopodin, and podocin were markedly decreased by 44%, and this was accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker staining, which is consistent with podocyte depletion. Staining for p57, synaptopodin, podocin, and DAPI increased at FSGS day 28 and was augmented by the ACE inhibitor enalapril, which is consistent with a partial replenishment of podocytes. In contrast, ZsGreen fluorescence did not return and remained significantly low at day 28, indicating replenishment was from a nonpodocyte origin. Despite administration of bromodeoxyuridine (BrdU) thrice weekly throughout the course of disease, BrdU staining was not detected in podocytes, which is consistent with an absence of proliferation. Although ZsGreen reporting was reduced in the tuft at FSGS day 28, labeled podocytes were detected along the Bowman's capsule in a subset of glomeruli, which is consistent with migration from the tuft. Moreover, more than half of the migrated podocytes coexpressed the parietal epithelial cell (PEC) proteins claudin-1, SSeCKS, and PAX8. These results show that although podocytes can be partially replenished following abrupt depletion, a process augmented by ACE inhibition, the source or sources are nonpodocyte in origin and are independent of proliferation. Furthermore, a subset of podocytes migrate to the Bowman's capsule and begin to coexpress PEC markers.

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Section: A B Cmentioning

confidence: 81%

Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources

Kaverina

Eng

Schneider

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Renal tubule epithelial cells play an indispensable part in glomerular filtration barrier [ 5 ]. The structural and functional integrity of renal tubule epithelial cells have close relation with the maintenance of glomerular filtration function [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Salusin-β protects renal tubular epithelial cells against high glucose-induced inflammation, oxidative stress, apoptosis and lipid accumulation via suppressing miR-155-5p

Chen

Jin

2021

Bioengineered

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Diabetic nephropathy (DN) is the main contributor to the excess mortality for patients suffering from diabetes. Here, C57BL/6 mice received 4 weeks of high-fat diet and intraperitoneal injection of STZ (100 mg/kg). Mice with random blood glucose level ≥16.7 mmol/L and positive urine protein were recognized as successful DN model. To construct an in vitro model, HK-2 cells were incubated with 30 mM glucose. RT-qPCR and western blot were employed to measure Salusin-β levels in kidney tissues of DN mice and HG-induced HK-2 cells. Meanwhile, RT-qPCR was performed to detect miR-155-5p level in kidney tissues of DN mice and HG-induced HK-2 cells. TNF-α, IL-6, IL-1β, ROS, SOD and CAT levels were assessed using commercial assay kits. Furthermore, apoptosis of HK-2 cells was assessed via flow cytometric analysis and TUNEL staining. In addition, intracellular lipid accumulation and total cholesterol levels were detected using Oil red O staining and TC ELISA kit. Herein, Salusin-β and miR-155-5p levels were distinctly upregulated in kidney tissues of DN mice and HG-induced HK-2 cells. Downregulation of Salusin-β reduced miR-155-5p expression. Salusin-β silencing dramatically relieved inflammatory and oxidative injury, suppressed apoptosis as well as lipid accumulation induced by HG in HK-2 cells. Besides, miR-155-5p elevation partially abrogated the alleviating effects Salusin-β silencing on HG-induced RTEC injury. In summary, downregulation of Salusin-β protected HK-2 cells against HG-induced inflammation, oxidative stress, apoptosis and ameliorated lipid accumulation through suppressing miR-155-5p, which indicated that Salusin-β could be a potential therapeutic drug for DN.

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“…We had 29 patients with confirmed detachment by routine light and electron microscopy. Their paraffin blocks were searched for any residual glomerular tissue to be stained by a special podocalyxin stain (colloidal iron) [ 16 – 18 ]. Of the nine patients who were eligible for this revision, the special stain confirmed detached cells in five of them, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, no study has discussed the ability of LM to detect podocyte detachment by routinely used stains. All the available studies discussed podocyte detachment as described with EM or by special stains or by counting all the currently available podocytes within the glomerulus [ 9 , 10 , 16 , 22 ]. We made the hypothesis that if we succeeded in confirming the ability of LM to detect detached podocytes, this would add a new, inexpensive, and easy method for in-depth evaluation of LM sections in patients with apparent MCD.…”

Section: Discussionmentioning

confidence: 99%

Role of detached podocytes in differentiating between minimal change disease and early focal segmental glomerulosclerosis, can we rely on routine light microscopy?

et al. 2022

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Background Detachment of podocytes represents a turning point in the development of glomerular sclerosis and consequently, of CKD progression. Furthermore, detachment may differentiate minimal change disease (MCD) cases—which have only podocyte effacement—from early focal segmental glomerulosclerosis (FSGS) in which effacement and detachment are observed by electron microscopy. Noteworthy, it is not uncommon for early FSGS to present with clinical presentation and light microscopy (LM) pictures identical to MCD. In our routine practice, we often find cells that lie freely in Bowman’s space by LM. In this study, we try to determine whether these cells are detached podocytes that are worth reporting or just an artifact that can be ignored. Methods To the best of our knowledge, no study has discussed the accuracy of LM in detecting detached podocytes by the routinely used stains. We retrospectively selected 118 cases that were diagnosed as MCD by LM, and searched for detached cells in Bowman’s space in their archived, routinely stained LM slides. After that, we tried to find any correlation between the clinical course, detached cells in LM picture and the EM reports. Results LM can significantly detect detached podocytes with a positive predictive value of 93%, specificity of 85%, and sensitivity of 46%. Significant correlations were found between detached cells and degree of proteinuria and late steroid resistance. Conclusion Detecting detached podocytes by LM is a specific finding that must be reported whenever detected, as it predicts response to steroids and may be able to differentiate MCD from early FSGS by identifying patients who could have podocytopenia.

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Assessment of detached podocytes in the Bowman's space as a marker of disease activity in lupus nephritis

Cited by 9 publications

References 7 publications

Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources

Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources

Downregulation of Salusin-β protects renal tubular epithelial cells against high glucose-induced inflammation, oxidative stress, apoptosis and lipid accumulation via suppressing miR-155-5p

Role of detached podocytes in differentiating between minimal change disease and early focal segmental glomerulosclerosis, can we rely on routine light microscopy?

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