Quantification of Changes in Transforming Growth Factor- 1 Gene Expression in Experimental Crescentic Glomerulonephritis

Lianos, Elias A.; Liu, Jim; Guglielmi, Kelly

doi:10.3181/00379727-214-44086

Cited by 4 publications

(4 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that PECs express PDGF receptor ␤, FGF receptor 1, and TGF-␤ receptors in vivo Floege et al, 1999;Matsuda et al, 1997;Yamamoto et al, 1998). Moreover, FGF-2 and PDGF-BB have been immunohistochemically localized in the crescents of anti-GBM nephritis in Wistar Kyoto rats (Fujigaki et al, 2001;Lianos et al, 1997). Growth factor-mediated PEC proliferation has been postulated in experimental glomerulonephritis.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (FGF)-2, and transforming growth factor (TGF)-␤ have been speculated to be involved in crescent formation by histologic studies on anti-glomerular basement membrane (GBM) glomerulonephritis (Fujigaki et al, 2001;Lianos et al, 1997;Ng et al, 1999). Moreover, TGF-␤ receptors, PDGF receptor ␤, and FGF receptor 1 have been shown to be expressed in PECs and crescents in humans Floege et al, 1999;Matsuda et al, 1997;Yamamoto et al, 1998).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Connective Tissue Growth Factor Participates in Scar Formation of Crescentic Glomerulonephritis

Kanemoto

Usui

Tomari

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY: Glomerular crescents are a major determinant of progression in various renal diseases. Some types of growth factors are known to be involved in the evolution of crescents and the subsequent scar formation. Although glomerular parietal epithelial cells (PECs) are the major component of cellular crescents, the influence of growth factors on PECs is unknown. We performed immunohistochemical studies and in situ hybridization to examine alterations in connective tissue growth factor (CTGF) expression and to identify CTGF-synthesizing cells in crescents in the crescentic glomerulonephritis model of Wistar Kyoto rats. In addition, we examined the roles of fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-␤, and CTGF in cell proliferation and matrix synthesis in an established rat PEC cell line (PEC line). In an acute phase of rat crescentic glomerulonephritis, a major component of the crescents were macrophages, which did not express CTGF mRNA. However, in the advanced phase, crescents strongly expressed CTGF mRNA and the epithelial marker pan-cadherin but did not express the macrophage marker ED1, suggesting that PECs synthesized the CTGF. In the PEC line, FGF-2 predominantly promoted [ 3 H]thymidine incorporation compared with PDGF-BB. Both TGF-␤ and PDGF-BB strongly stimulated extracellular matrix synthesis in association with up-regulation of endogenous CTGF, but TGF-␤ showed a predominant role. FGF-2 had a minor effect on it. In addition, blockade of endogenous CTGF using an antisense oligodeoxynucleotide significantly attenuated both TGF-␤-and PDGF-BB-induced extracellular matrix synthesis. These results suggest that several growth factors promote cell proliferation and matrix production in PECs. CTGF-mediated matrix production via the TGF-␤ or PDGF-BB pathway in PECs may, in part, play a role in the progression of scar formation in crescents. (Lab Invest 2003, 83:1615-1625.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Connective Tissue Growth Factor Participates in Scar Formation of Crescentic Glomerulonephritis

Kanemoto

Usui

Tomari

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…In this process the cell cycles of macrophages and myofibroblasts, both of which are key cells in fibrogenesis, should be regulated by CDKI and also by profibrogenic cytokines, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β. Indeed, TGF-β is reported to be involved in the fibrous progression of the crescent formation [13,16].…”

Section: Introductionmentioning

confidence: 99%

Cytokines and cell cycle regulation in the fibrous progression of crescent formation in antiglomerular basement membrane nephritis of WKY rats

et al. 2001

View full text Add to dashboard Cite

Cytokines may regulate cell proliferation by cell-cycle-regulatory proteins, in which cyclin-dependent kinase inhibitors (CDKI) inhibit cell proliferation. We investigated whether CDKI p21 or p27, both of which are potentially regulated by transforming growth factor (TGF)-beta, a key cytokine in fibrogenesis, are involved together with TGF-beta and/or platelet-derived growth factor (PDGF) in the fibrous progression of glomerular crescent formation and examined the sequential change in the cell type and the cellular background of myofibroblasts in crescent formation. Crescentic glomerulonephritis (GN) was induced by i.v. injection of rabbit antirat glomerular basement membrane antiserum in WKY rats. Animals were killed 1, 2, 3 and 4 weeks after the induction of GN, and their kidneys were processed for immunohistochemical examination. After 1 week more than 85% of glomeruli showed cellular crescents, which became fibrocellular with decreased cellularity by 4 weeks. ED 1-positive macrophages were components of crescent cells in about 44% at 1-2 weeks, and this proportion declined markedly afterwards. Alpha smooth muscle actin (alpha SMA, a marker for myofibroblasts)-positive cells were found in Bowman's epithelial cells (BEP) and in some crescent cells at 1 week, becoming major components of crescent cells by 4 weeks (about 40%). It was 2 weeks before invasion of alpha SMA-positive interstitial cells into glomeruli was evident. PDGF-B and PDGF receptor beta-positive cells, indicating possible targets for PDGF, were found in BEP adjoining crescent formation almost exclusively from 1 to 2 weeks. By contrast, both TGF-beta receptor types I- and II-positive cells, indicating possible effectors for TGF-beta, were found in BEP and crescent formation, and the percentage of these in the crescent formation did not change until 4 weeks (about 32%). Cells with positive immunostaining for proliferating cell nuclear antigen and cyclin A, markers for cell proliferation, in the crescent formation peaked in number and proportion at 1-2 weeks, then decreased. In contrast, cells with positive immunostaining for p21 and p27, CDKI, were sparse at 1 week, and then increased markedly in number and in proportion, peaking at 3 (39.6%) or 2-3 weeks (about 25-30%), respectively. The present study demonstrates that restrained expression or a transient increase in p21 and p27 may be associated with proliferation or with inhibited proliferation of crescent cells, most of which are macrophages and myofibroblasts. The action, of PDGF and TGF-beta may contribute to the recruitment of myofibroblasts into the crescent. The action of TGF-beta on crescent cells might be linked to the expression of p21 and/or p27.

show abstract

“…The GAPDH primers were as follows: forward, 5Ј-GTGCTGAG-TATGTCGTGGA-3Ј; reverse, 5Ј-CACAGTCTTCGAGTGGCA-3Ј. These primers yield a PCR product of 298 bp (22).…”

Section: Quantification Of Glomerular Inos and Ho-1 Mrna Levels By Reverse Transcription-pcrmentioning

confidence: 99%

Heme Oxygenase-1 Induction Attenuates Inducible Nitric Oxide Synthase Expression and Proteinuria in Glomerulonephritis

Datta¹,

Koukouritaki²,

Hopp³

et al. 1999

Journal of the American Society of Nephrology

102

View full text Add to dashboard Cite

Abstract. In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 μmol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 μM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.

show abstract

Quantification of Changes in Transforming Growth Factor- 1 Gene Expression in Experimental Crescentic Glomerulonephritis

Cited by 4 publications

References 1 publication

Connective Tissue Growth Factor Participates in Scar Formation of Crescentic Glomerulonephritis

Connective Tissue Growth Factor Participates in Scar Formation of Crescentic Glomerulonephritis

Cytokines and cell cycle regulation in the fibrous progression of crescent formation in antiglomerular basement membrane nephritis of WKY rats

Heme Oxygenase-1 Induction Attenuates Inducible Nitric Oxide Synthase Expression and Proteinuria in Glomerulonephritis

Contact Info

Product

Resources

About