Primary Cultures of Glomerular Parietal Epithelial Cells or Podocytes with Proven Origin

Kabgani, Nazanin; Grigoleit, Tamara; Schulte, Kevin; Sechi, Antonio; Sauer-Lehnen, Sibille; Tag, Carmen G.; Boor, Peter; Kuppe, Christoph; Warsow, Gregor; Schordan, Sandra; Mostertz, Jörg; Chilukoti, Ravi Kumar; Homuth, Georg; Endlich, Nicole; Tacke, Frank; Weiskirchen, Ralf; Fuellen, Georg; Endlich, Karlhans; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J.

doi:10.1371/journal.pone.0034907

Cited by 55 publications

(52 citation statements)

References 29 publications

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“…These eGFP-labeled cells expressed increased amounts of the podocyte marker Wilms tumor 1 (WT-1) compared with the relatively low expression of WT-1 in PECs, which has been described previously. 21 These results also support that these cells Juxtamedullary glomeruli, which develop sooner than the cortical glomeruli, rarely showed synaptopodin-positive PECs on Bowman's capsule (data not shown). The PEC-rtTA/ H2B-eGFP reporter line marked about 80% of all cells on Bowman's capsule, similar to the labeling frequency in adult mice 12 ( Figure 6E), regardless of their coexpression of podocyte marker proteins.…”

Section: Recruitment Of Podocytes From Cells On Bowman's Capsule In Jsupporting

confidence: 70%

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Berger¹,

Schulte²,

Kuppe³

et al. 2014

Journal of the American Society of Nephrology

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Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman's capsule expressed podocyte markers, and cells on Bowman's capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman's capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman's capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman's capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans.

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Section: Recruitment Of Podocytes From Cells On Bowman's Capsule In Jsupporting

confidence: 70%

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Berger¹,

Schulte²,

Kuppe³

et al. 2014

Journal of the American Society of Nephrology

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“…It has been reported that the PAX-2 protein is normally restricted to PECs in the glomerulus (11). PAX-2 immunostaining was observed in all groups ( Figure 2B).…”

Section: Number Of Cells Expressing Pax-2 Protein Along the Bbm In Easupporting

confidence: 57%

Islet transplantation promotes podocyte regeneration in a model of diabetic nephropathy

Fan¹

2017

Turk J Med Sci

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IntroductionDiabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) and accounts for more than 25% of all ESRD cases in China (1,2). The initiation and progression of DN is associated with podocyte injury and loss. It has been reported that the podocyte population can be restored and that this process is linked to the regression of DN (3).Islet transplantation (IT) and pancreas transplantation are the most effective measures to counteract type 1 diabetes (4,5). It has been reported that IT can ameliorate albuminuria and alleviate damage to the kidney (6). We have previously demonstrated that IT can directly modify the barrier of glomerular filtration by ameliorating damage to the podocytes and the glomeruli basement membrane (7). However, the mechanisms that underlie how the barrier for glomerular filtration improves currently remain elusive.Recent studies have demonstrated that podocytes can regenerate from parietal epithelial cell (PEC) progenitors in human DN and in a diabetic mouse model (8,9).In this study, we examined whether IT induces PECs to express podocyte proteins. The amelioration of the structure and function of podocytes is a crucial factor in the process of recovery of early diabetic nephropathy. Thus, an increased focus on podocytes may be beneficial in the treatment of DN in clinical practice. Materials and methods AnimalsThis experimental study was conducted at Wenzhou Medical University. Thirty-six male Sprague Dawley (SD) rats at 8 weeks of age (body weight: 200-220 g) were obtained from the Laboratory Animal Center of Wenzhou Medical University. Eighteen of these rats were used to establish the DN models and the others were used as donor rats. All rats were housed with a 12:12-h light/dark cycle Background/aim: The purpose of this study was to observe whether islet transplantation could induce glomerular parietal epithelial cells to express podocyte proteins in a rat model of streptozotocin-induced diabetic nephropathy (DN). Materials and methods:A total of 18 rats were given single injections of streptozotocin to induce a DN model. Eight weeks after the modeling, successfully established DN rats were divided into three groups: an untreated group (DN group), an islet-transplanted group (IT group), and an insulin group (IN group). The islets cells were isolated from donor rats and surgically transplanted from under the kidney capsule in the IT group. Four weeks after treatment, pathological changes in the kidney were observed by pathological staining and electron microscopy. Immunohistochemical staining for PAX-2, Ki-67, and synaptopodin was performed to evaluate cell proliferation in the kidney tissues.Results: After 4 weeks of treatment, islet transplantation significantly alleviated damage to the podocytes and increased the number of glomerular transition cells compared to the DN and IN groups, which were defined as cells that double-stained for PAX-2 and synaptopodin in membranous nephropathy. The results of HE staining, PAS staining, and electron microscopy d...

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“…To analyze the regulation and cellular effects of CD74 and MIF, we used our recently developed primary cultures of murine podocytes and PECs with proven origin 31 and the well established cultures of primary mesangial cells. 32,33 Flow-cytometric analyses of the primary cultures showed that PECs, podocytes, and mesangial cells expressed CD74, whereas only PECs and mesangial cells coexpressed CD44 ( Figure 3A), confirming our in vivo immunohistochemic data.…”

Section: Mif Receptor Expression In Glomerular Cells In Vitromentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

Djudjaj¹,

Lue

Rong³

et al. 2015

JASN

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Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow-derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN.

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Primary Cultures of Glomerular Parietal Epithelial Cells or Podocytes with Proven Origin

Cited by 55 publications

References 29 publications

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Islet transplantation promotes podocyte regeneration in a model of diabetic nephropathy

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

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