Hepatocyte growth factor and its receptor Met are induced in crescentic glomerulonephritis

Rampino, Teresa; Gregorini, Marilena; Camussi, Giovanni; Conaldi, Pier Giulio; Soccio, Grazia; Maggio, Milena; Bottelli, Antonella; Canton, Antonio Dal

doi:10.1093/ndt/gfh740

Cited by 18 publications

(21 citation statements)

References 18 publications

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“…2,3,8 Previous studies have concluded that the most numerous cell is the parietal epithelial cell, 1,2,7 with varying numbers of macrophages depending on the severity of the glomerular disease. 3,4 However, in these studies, the epithelial cell that is the most abundant component in crescents has been assumed to be a parietal epithelial cell, largely because no podocyte marker can be identified. 8 We think that the nestin-positive cells in crescents are podocytic in origin for several reasons.…”

Section: Discussionmentioning

confidence: 99%

“…3 Parietal epithelial cells are usually identified as such by antibodies to keratin and macrophages by CD68 immunostaining. 1,2,4 However, the picture is an incomplete one because some studies have found that macrophages constitute only a small proportion of the cells in crescents, 2,3 a finding supported by studies in animal models. 5,6 Moreover, there exists a population of cells in crescents that appear to be epithelial by morphology but are keratin-negative, 4,7 sometimes comprising the most abundant cell in the crescent.…”

mentioning

confidence: 99%

“…1,2,4 However, the picture is an incomplete one because some studies have found that macrophages constitute only a small proportion of the cells in crescents, 2,3 a finding supported by studies in animal models. 5,6 Moreover, there exists a population of cells in crescents that appear to be epithelial by morphology but are keratin-negative, 4,7 sometimes comprising the most abundant cell in the crescent. These cells have been assumed to be parietal epithelial cells, but this assumption is not based on the demonstration of any markers specific for parietal epithelial cells.…”

mentioning

confidence: 99%

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Podocytes Contribute to the Formation of Glomerular Crescents

Thorner¹,

Ho²,

Eremina³

et al. 2008

Journal of the American Society of Nephrology

115

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The cellular composition of crescents in glomerular disease is controversial. The role of podocytes in crescent formation has been especially difficult to study because podocytes typically lose their characteristic terminally differentiated phenotype under disease conditions, making them difficult to identify. We reasoned that the intermediate filament protein nestin, a marker of progenitor cells that has recently been identified in podocytes, may allow the investigation of podocyte involvement in glomerular crescents. In a series of 35 biopsies with crescentic glomerular disease, all showed nestin-positive cells in the crescents, ranging in number from occasional to approximately 50% of crescent cells. Other podocyte markers, such as podocin and WT1, failed to identify cells in crescents, and no contribution by endothelial or myogenic cells was noted. CD68-positive cells were observed in 80% of cases but were never as numerous as the nestin-positive cells. Nestin and CD68 were not coexpressed by the same cells, providing no evidence of trans-differentiation of podocytes into a macrophage phenotype. Keratinpositive cells were found in crescents in 51% of cases, but only as occasional cells. Up to one third of crescent cells were cycling in 48% of biopsies, and double immunostaining identified these cells as a mixture of nestin-positive cells and "null" cells (negative for nestin, CD68, and keratin). In addition to our observations in human disease, we also identified nestin-positive proliferating podocytes in the crescents of 2 mouse models of crescentic glomerulonephritis. We conclude that podocytes play a role in the formation of glomerular crescents.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Podocytes Contribute to the Formation of Glomerular Crescents

Thorner¹,

Ho²,

Eremina³

et al. 2008

Journal of the American Society of Nephrology

115

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“…Recently, we found that hepatocyte growth factor (HGF), a putative de-differentiation factor of podocytes [21], markedly suppressed activity of the nephrin gene promoter (Supplemental Fig. 2A) as well as expression of nephrin mRNA (Supplemental Fig.…”

Section: Molecular Mechanisms Involved In Transcriptionalmentioning

confidence: 99%

Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

et al. 2007

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Expression of nephrin, a crucial component of the glomerular slit diaphragm, is downregulated in patients with proteinuric glomerular diseases. Using conditionally immortalized reporter podocytes, we found that bystander macrophages as well as macrophage-derived cytokines IL-1b and TNF-a markedly suppressed activity of the nephrin gene promoter in podocytes. The cytokine-initiated repression was reversible, observed on both basal and inducible expression, independent of Wilms' tumor suppressor WT1, and caused in part via activation of the phosphatidylinositol-3-kinase/Akt pathway. These results indicated a novel mechanism by which activated macrophages participate in the induction of proteinuria in glomerular diseases.

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“…This limits future therapeutic options aimed at stimulation of HGF secretion or activation of Met to prevent podocyte loss in renal transplants. Besides the potential unwanted effect of mesangioproliferation, increased Met signaling has been shown to be involved in crescent formation, 81 proteinuria, 82 and down-regulation of nephrin. 83 Met is also known as a proto-oncogene, 84 linked to hereditary papillary renal cell carcinoma 85 and other neoplasms.…”

Section: Discussionmentioning

confidence: 99%

Diminished Met Signaling in Podocytes Contributes to the Development of Podocytopenia in Transplant Glomerulopathy

Agustian

Schiffer

Gwinner

et al. 2011

The American Journal of Pathology

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Hepatocyte growth factor and its receptor Met are induced in crescentic glomerulonephritis

Abstract: These results suggest that HGF/Met system participates in the process of crescent formation by inducing podocyte migration, growth and mesenchymal transformation.

Cited by 18 publications

References 18 publications

Podocytes Contribute to the Formation of Glomerular Crescents

Podocytes Contribute to the Formation of Glomerular Crescents

Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

Diminished Met Signaling in Podocytes Contributes to the Development of Podocytopenia in Transplant Glomerulopathy

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