Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

Pabst, Reinhard; Sterzel, R. Bernd

doi:10.1038/ki.1983.203

Cited by 207 publications

(113 citation statements)

References 11 publications

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“…35 In the present study, the dramatic upregulation of CCPs observed in glomerular endothelium of human IgAN biopsy specimens suggests a substantially increased turn-over rate of glomerular endothelial cells in addition to mesangial cell proliferation. The increase in CDK2 expression by glomerular endothelium observed in IgAN together with the increased CDK2 expression during mesangial cell proliferation reported in anti-Thy1.1 nephritis, 3 support the notion that the in vivo expression of certain cell cycle proteins may differ from that described in nonrenal cells studied in vitro.…”

Section: Discussionmentioning

confidence: 72%

Role of differential and cell type-specific expression of cell cycle regulatory proteins in mediating progressive glomerular injury in human IgA nephropathy

Qiu

Sinniah

Hsu

2004

Laboratory Investigation

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The activities of cell cycle regulatory proteins have been reported to be associated with the development of pathological lesions in glomerulonephritis. To assess the cellular mechanisms underlying the mesangial cell proliferation and glomerulosclerosis in progressive human IgA nephropathy (IgAN), we examined the expression of E2F1, Rb, c-Myc, proliferating cell nuclear antigen (PCNA), cyclins (D1, E and A), cyclindependent kinase 2 (CDK2) and CDK inhibitors (p21 waf1 , p27 kip1 , 57 kip2 and p16 ink4a ) by immunohistochemistry in renal biopsy specimens. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was also performed to detect the presence of apoptosis. In total, 51 cases of IgAN were categorized into four subgroups according to histological severity. A dramatic upregulation of E2F1 expression in mesangial cells was identified in proliferating glomeruli, which correlated well with the proliferation index. High endogenous expression of p27 kip1 and p57 kip2 by podocytes in normal glomeruli and glomeruli with minor lesions was observed to decrease in proliferating and sclerosing glomeruli; this pattern displayed a strong inverse correlation with the mean glomerulosclerosis score and the index of glomerular lesion. Increased apoptotic activity was identified in progressive glomerular lesions of advanced IgAN, which correlated with the proliferative activity in these lesions as assessed by total expression levels of PCNA and CDK2 in glomeruli, E2F1 expression levels in the mesangium, cyclin D1 expression levels in endothelium and the c-Myc glomerular staining score. Our results suggest that the onset and magnitude of mesangial cell proliferation and glomerulosclerosis is associated with the upregulation of E2F1 by mesangial cells and the downregulation of p27 kip1 and p57 kip2 by glomerular epithelial cells. The cell type-specific and coordinated regulation of proliferative and proapoptotic activities of cell cycle regulatory proteins may play an important role in mediating progressive glomerular injury in human IgAN. Laboratory Investigation (2004) 84, 1112-1125, advance online publication, 21 June 2004 doi:10.1038/labinvest.3700144 Keywords: IgA nephropathy; cell cycle regulatory protein; mesangial cell proliferation; glomerulosclerosis; apoptosis Cell cycle regulatory proteins (CCPs) govern not only cellular hypertrophy and proliferation, but also cellular apoptosis and differentiation. Mounting evidence has emerged that indicates a close link between cell cycle regulation and the development of histopathological lesions in glomerular diseases. 1,2 In the experimental model of mesangial proliferative anti-Thy1.1 nephritis, increased expression of cyclins A, D1 and cyclin-dependent kinase 2 (CDK2) by mesangial cells in association with decreased high endogenous levels of CDK inhibitor (CKI) p27 kip1 by glomerular epithelial cells (GECs), were required for mesangial cell proliferation. [3][4][5] The increased glomerular activity of CDK2 could be inhibited by the CDK antagonist r...

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Section: Discussionmentioning

confidence: 72%

Role of differential and cell type-specific expression of cell cycle regulatory proteins in mediating progressive glomerular injury in human IgA nephropathy

Qiu

Sinniah

Hsu

2004

Laboratory Investigation

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“…In support of this is the estimate of 1% daily renewal made by Pabst and Sterzel. 12 Although we observed mesangial cells in all 5 mice revealing clonal hematopoietic engraftment, these numbers are too small to answer the question of whether or not all hematopoietic stem cells are capable of generating mesangial cells. Analysis of kidneys from mice receiving transplants of paired progenies of stem cells is in progress to examine the mechanisms of stem cell commitment to the mesangial cell lineage.…”

Section: Discussionmentioning

confidence: 84%

Hematopoietic origin of glomerular mesangial cells

Masuya

Drake

Fleming

et al. 2003

Blood

164

138

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“…Previously, autoradiographic studies have demonstrated low rates of glomerular mesangial and endothelial cell proliferation in control rats, indicating low but constant rates of glomerular cell renewal of about 1% per day. 28 Our data suggest that bone-marrow-derived cells contribute to normal physiological glomerular-endothelial and mesangial cell turnover.…”

Section: Discussionmentioning

confidence: 89%

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

Rookmaaker

Smits

Tolboom

et al. 2003

The American Journal of Pathology

160

122

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Glomerular endothelial injury plays an important role in the pathogenesis of renal diseases and is centrally involved in renal disease progression. Glomerular endothelial repair may help maintain renal function. We examined whether bone-marrow (BM)-derived cells contribute to glomerular repair. A rat allogenic BM transplant model was used to allow tracing of BM-derived cells using a donor major histocompatibility complex class-I specific mAb. In glomeruli of chimeric rats we identified a small number of donor-BM-derived endothelial and mesangial cells, which increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis (transient mesangial and secondary glomerular endothelial injury) caused a significant, more than fourfold increase in the number of BM-derived glomerular endothelial cells at day 7 after anti-Thy-1.1 injection compared to chimeric rats without glomerular injury. The level of BM-derived endothelial cells remained high at day 28. We also observed a more than sevenfold increase in the number of BM-derived mesangial cells at day 28. BM-derived endothelial and mesangial cells were fully integrated in the glomerular structure. Our data show that BM-derived cells participate in glomerular endothelial and mesangial cell turnover and contribute to microvascular repair. These findings provide novel insights into the pathogenesis of renal disease and suggest a potential role for stem cell therapy.

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Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

Cited by 207 publications

References 11 publications

Role of differential and cell type-specific expression of cell cycle regulatory proteins in mediating progressive glomerular injury in human IgA nephropathy

Role of differential and cell type-specific expression of cell cycle regulatory proteins in mediating progressive glomerular injury in human IgA nephropathy

Hematopoietic origin of glomerular mesangial cells

Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis

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