Origin and phenotypic features of hyperplastic epithelial cells in collapsing glomerulopathy

Nagata, Michio; Hattori, Motoshi; Hamano, Yukako; Ito, Katsuhiko; Saitoh, K; Watanabe, Teruo

doi:10.1016/s0272-6386(98)70070-8

Cited by 61 publications

(42 citation statements)

References 22 publications

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“…The alterations seen in podocyte damage in the p21 and p27 Ϫ/Ϫ mice resembled the human glomerular diseases with podocyte proliferation, namely, HIV nephropathy (31), collapsing glomerulopathy (298,472), and the cellular variant of focal-segmental glomerulosclerosis (80). Intact human podocytes differ from murine podocytes in that they do not express p21 but show a robust signal for p27 and p57 (70,300,415).…”

Section: Set Of Glomerular Diseasesmentioning

confidence: 91%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,308

1,278

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Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

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Section: Set Of Glomerular Diseasesmentioning

confidence: 91%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,308

1,278

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“…However, a role for PECs in this sclerotic process has emerged over recent years as follows. In the era predating currently used cell fate mapping techniques, several well performed studies using immunostaining for cell 'specific' markers showed the presence of PECs within sclerotic areas in experimental and human disease [36,37]. These studies suggested that PECs might participate in the focal sclerotic glomerular process.…”

Section: Parietal Epithelial Cells and Glomerular Scarringmentioning

confidence: 99%

Glomerular parietal epithelial cells in kidney physiology, pathology, and repair

Shankland

Anders

Romagnani

2013

Current Opinion in Nephrology and Hypertension

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Purpose of reviewWe have summarized recently published glomerular parietal epithelial cell (PEC) research, focusing on their roles in glomerular development and physiology, and in certain glomerular diseases. The rationale is that PECs have been largely ignored until the recent availability of cell lineage tracing studies, human and murine PEC culture systems, and potential therapeutic interventions of PECs. Recent findingsSeveral new paradigms involving PECs have emerged demonstrating their significant contribution to glomerular physiology and numerous glomerular diseases. A subset of PECs serving as podocyte progenitors have been identified in normal human glomeruli. They provide a source for podocytes in adolescent mice, and their numbers increase in states of podocyte depletion. PEC progenitor number is increased by retinoids and angiotensin-converting enzyme inhibition. However, dysregulated growth of PEC progenitors leads to pseudo-crescent and crescent formation. In focal segmental glomerulosclerosis, considered a podocyte disease, activated PECs increase extracellular matrix production, which leads to synechial attachment and, when they move to the glomerular tuft, to segmental glomerulosclerosis. Finally, PECs might be adversely affected in proteinuric states by undergoing apoptosis. SummaryPECs play a critical role in glomerular repair through their progenitor function, but under certain circumstances paradoxically contribute to deterioration by augmenting scarring and crescent formation.

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“…15 By contrast, we and another group have observed the expression of the PEC markers cytokeratin and Pax-2 in these lesions. 16,17 Because immunostaining studies to identify cell markers are insufficient to determine cellular origin, whether visceral cell hyperplasia is the result of podocytes that have lost their podocyte markers and are expressing PEC markers de novo, or proliferating PECs that persistently express their own markers remains unclear. The interactions between two resident epithelial cells that mimic glomerulogenesis (ie, cell proliferation and phenotypic alterations) may play a key role in the progression of FSGS.…”

mentioning

confidence: 99%

Genetic Podocyte Lineage Reveals Progressive Podocytopenia with Parietal Cell Hyperplasia in a Murine Model of Cellular/Collapsing Focal Segmental Glomerulosclerosis

Suzuki

Matsusaka

Nakayama

et al. 2009

The American Journal of Pathology

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Focal segmental glomerulosclerosis (FSGS) is a progressive renal disease, and the glomerular visceral cell hyperplasia typically observed in cellular/collapsing FSGS is an important pathological factor in disease progression. However, the cellular features that promote FSGS currently remain obscure. To determine both the origin and phenotypic alterations in hyperplastic cells in cellular/collapsing FSGS, the present study used a previously described FSGS model in p21-deficient mice with visceral cell hyperplasia and identified the podocyte lineage by genetic tagging. The p21-deficient mice with nephropathy showed significantly higher urinary protein levels, extracapillary hyperplastic indices on day 5, and glomerular sclerosis indices on day 14 than wild-type controls. X-gal staining and immunohistochemistry for podocyte and parietal epithelial cell (PEC) markers revealed progressive podocytopenia with capillary collapse accompanied by PEC hyperplasia leading to FSGS. In our investigation, non-tagged cells expressed neither WT1 nor nestin. Ki-67, a proliferation marker, was rarely associated with podocytes but was expressed at high levels in PECs. Both terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and electron microscopy failed to show evidence of significant podocyte apoptosis on days 5 and 14. These findings suggest that extensive podocyte loss and simultaneous PEC hyperplasia is an actual pathology that may contribute to the progression of cellular/collapsing FSGS in this mouse model. Additionally, this is the first study to demonstrate the regulatory role of p21 in the PEC cell cycle. (Am J

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Origin and phenotypic features of hyperplastic epithelial cells in collapsing glomerulopathy

Cited by 61 publications

References 22 publications

Cell Biology of the Glomerular Podocyte

Cell Biology of the Glomerular Podocyte

Glomerular parietal epithelial cells in kidney physiology, pathology, and repair

Genetic Podocyte Lineage Reveals Progressive Podocytopenia with Parietal Cell Hyperplasia in a Murine Model of Cellular/Collapsing Focal Segmental Glomerulosclerosis

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