Deduction from Wilms' tumour that glomerular podocytes produce the basement membrane material bearing goodpasture determinants

Droz, Dominique; Diebold, N.; Jan, Dominique; Jaubert, Françis

doi:10.1002/path.1711620408

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…27 Another study examined sections of Wilms tumor and showed that the avascular glomeruloid bodies were labeled with antibodies against Goodpasture determinants (previously shown to be structural motifs located specifically on the NC1 domain of the ␣3 chain of collagen IV), 16,28 providing additional evidence that this protein is a product of podocytes. 29 Although results from cultured immortalized podocytes need to be interpreted carefully, experiments have also shown that these cells synthesize ␣3(IV) collagen in vitro. For example, addition of exogenous vascular endothelial growth factor (VEGF) to immortalized mouse podocytes increases the production of collagen ␣3(IV), and this is reversed by treatment with the VEGF receptor inhibitor, SU5416.…”

Section: Discussionmentioning

confidence: 99%

Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

Abrahamson

Hudson²,

Stroganova³

et al. 2009

Journal of the American Society of Nephrology

181

148

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Laminin and type IV collagen composition of the glomerular basement membrane changes during glomerular development and maturation. Although it is known that both glomerular endothelial cells and podocytes produce different laminin isoforms at the appropriate stages of development, the cellular origins for the different type IV collagen heterotrimers that appear during development are unknown. Here, immunoelectron microscopy demonstrated that endothelial cells, mesangial cells, and podocytes of immature glomeruli synthesize collagen ␣1␣2␣1(IV). However, intracellular labeling revealed that podocytes, but not endothelial or mesangial cells, contain collagen ␣3␣4␣5(IV). To evaluate the origins of collagen IV further, we transplanted embryonic kidneys from Col4a3-null mutants (Alport mice) into kidneys of newborn, wildtype mice. Hybrid glomeruli within grafts containing numerous host-derived, wildtype endothelial cells never expressed collagen ␣3␣4␣5(IV). Finally, confocal microscopy of glomeruli from infant Alport mice that had been dually labeled with anti-collagen ␣5(IV) and the podocyte marker anti-GLEPP1 showed immunolabeling exclusively within podocytes. Together, these results indicate that collagen ␣3␣4␣5(IV) originates solely from podocytes; therefore, glomerular Alport disease is a genetic defect that manifests specifically within this cell type. Basement membranes are thin sheets of extracellular matrix that underlie epithelial cells, including the vascular endothelium, and surround all muscle cells, Schwann cells, and adipocytes. They are composed of polymers of laminin and type IV collagen, and also contain nidogen/entactin, and proteoglycans. During glomerulogenesis, a basement membrane beneath developing endothelial cells fuses with a separate basement membrane layer beneath differentiating podocytes, to produce the glomerular basement membrane (GBM) shared on opposing surfaces by both cell types. 1 Unlike most basement membranes in the body, the laminin and collagen IV composition of the GBM changes temporally as the glomerulus develops. 2 The earliest GBMs of comma-and S-shaped nephrons contain laminin ␣1␤1␥1 (laminin 111), whereas those at later developmental stages and in adulthood contain laminin ␣5␤2␥1 (laminin 521). 2,3 Previously, we showed by postfixation immunoelectron microscopy that both endothelial cells and podocytes synthesize laminin ␣1 and ␤1 initially, and both cells then undergo a laminin isoform switch and synthesize laminin ␣5 and ␤2 as glomeruli mature. 4 The mechanism and reason why laminin replacement occurs are unknown, but

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Section: Discussionmentioning

confidence: 99%

Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

Abrahamson

Hudson²,

Stroganova³

et al. 2009

Journal of the American Society of Nephrology

181

148

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“…Note that in rats CD10 is expressed on PECs, whereas in humans CD10 is expressed on podocytes and proximal tubules. 11,12 Narp protein was neither detected in monocytes/macrophages using ED1, nor in apoptotic cells using antibodies against active Caspase 3 (Figure 5e and f respectively).…”

Section: Identification Of Narp-positive Cells In Glomerulimentioning

confidence: 96%

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

Aben

IJpelaar

Baelde

et al. 2006

Kidney International

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Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

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“…Wilms tumor retains some features of the different steps of metanephric kidneys, including those of glomeruloid bodies similar to glomeruli 12,13 . Previous studies have shown that glomeruloid bodies in WMT express several markers for podocytes, including CALLA, CR1, and vimentin 14–17 16,17 .…”

mentioning

confidence: 98%

“…Previous studies have shown that glomeruloid bodies in WMT express several markers for podocytes, including CALLA, CR1, and vimentin 14–17 16,17 . However, the differentiation status of podocytes is better tested by examining the combined expression of recently identified specific markers for podocytes, such as WT1, synaptopodin or nephrin, and the functional structures such as foot processes or slit diaphragms 18–21 …”

mentioning

confidence: 99%

Variable expression of podocyte‐related markers in the glomeruloid bodies in Wilms tumor

Kanemoto

Takahashi

Shu

et al. 2003

Pathology International

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Several podocyte-related markers are organized to express in glomerular differentiation. However, whether expression of them is virtually synchronized and a reliable indicator of the state of differentiation is unknown. The present study investigated, by immunohistochemistry, the divergent expression of several podocyte markers in the improperly differentiated glomeruloid bodies from four cases of Wilms tumors. The glomeruloid bodies were classified into immature (IGB) or mature forms (MGB) based on morphology and epithelial features. Podocytes in IGB expressed WT1, synaptopodin, podocalyxin, and nephrin, and their expression was stronger in MGB. In contrast, Pax2 was strong in IGB and diminished in MGB. p27 was first expressed in MGB. The expression pattern in each molecule mimics normal glomerulogenesis. Podocytes in MGB showed persistent expression of bcl-2 and cytokeratin with synaptopodin, podocalyxin, and nephrin by serial section, a finding unusual for normal glomerulogenesis. Moreover, parietal cells in MGB also occasionally expressed these podocyte markers. The ultrastructure revealed that podocytes in MGB showed tight junctions without foot process formations, which indicated incomplete differentiation. These results suggest that a set of podocyte differentiation markers are occasionally diversely expressed, and raise the possibility that expression of these markers is insufficient to determine the state of terminal differentiation in podocytes.

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Deduction from Wilms' tumour that glomerular podocytes produce the basement membrane material bearing goodpasture determinants

Cited by 7 publications

References 9 publications

Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

Cellular Origins of Type IV Collagen Networks in Developing Glomeruli

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis

Variable expression of podocyte‐related markers in the glomeruloid bodies in Wilms tumor

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