Heparin-binding EGF-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats

Li, Feng; García, Georgia Earnest; Yang, Young Mok; Xia, Ying; Gabbai, Francis B.; Peterson, O. W.; Abraham, Judith A.; Blantz, Roland C.; Wilson, Curtis B.

doi:10.1172/jci2869

Cited by 36 publications

(40 citation statements)

References 67 publications

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“…These factors include heparin-binding epidermal growth factor-like growth factor (HB-EGF; Feng et al 2000;Polihronis et al 1996), platelet-derived growth factor (PDGF; Abboud 1995;Eitner et al 2003), connective tissue growth factor (CTGF; Ito et al 2001), and transforming growth factor-b (TGF-b; Ito et al 2001). These growth factors are well known for their potential to induce a migratory phenotype in various cell types through reorganization of the actin cytoskeleton (Matsumoto et al 1999;Moussad and Brigstock 2000;Raab and Klagsbrun 1997;Zavadil et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Besse-Eschmann

Hir

Endlich

et al. 2004

Histochem Cell Biol

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Recent observations suggest a central role of podocytes in crescent formation. In experimental glomerulonephritis podocytes disrupt the parietal epithelial layer and attach on its basement membrane, thus forming bridges between the tuft and Bowman's capsule, and they are a major constituent of crescents. In order to explain these findings we hypothesize that inflammation triggers motility in podocytes. In the present study we asked whether podocytes display alterations which suggest a migratory behavior in glomerulonephritis. Glomerulonephritis was induced in mice by injection of a rabbit serum against the glomerular basement membrane. The kidneys were perfusion-fixed 6 days later and examined by light and electron microscopy as well as by immunohistochemistry. In glomerulonephritis the apical cytoplasm of podocytes displayed numerous actin-containing microprotrusions. Cortactin, a protein involved in the regulation of actin polymerization, was predominantly expressed in foot processes of podocytes in control mice. It was redistributed to the cell body in glomerulonephritis. In untreated mice betal-integrin was restricted to the foot processes. In glomerulonephritis it was additionally found in the cytoplasm and in the apical cell membrane. Recycling of integrins is a crucial event in initiation of cell migration. ICAM-1 and CD44, the ligation of which induces migratory behaviors, were absent from healthy podocytes but expressed by some podocytes in glomerulonephritis. Thus, in glomerulonephritis podocytes display some characteristic features of migrating cells. This might explain their ability to break through the parietal epithelium and to become a constituent of early crescents.

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Section: Discussionmentioning

confidence: 99%

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Besse-Eschmann

Hir

Endlich

et al. 2004

Histochem Cell Biol

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“…Three µg of total RNA from each sample was used in an RNase protection assay using the Torrey Pines Biolabs kit (Houston, TX) as described (11,16,42,43). Phosphoimage quantitiation was performed using the PhosphorImager SI scanning instrument and ImageQuaNT software (Molecular Dynamics, Sunnyvale, CA) (16,44,45).…”

Section: Induction Treatment and Analysis Of Anti-gbm Glomerulonephmentioning

confidence: 99%

Adenosine A_2Areceptor activation and macrophage‐mediated experimental glomerulonephritis

García¹,

Truong²,

Li³

et al. 2007

FASEB j.

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In immune-induced inflammation, leukocytes are key mediators of tissue damage. Since A 2A adenosine receptors (A 2A R) are endogenous suppressors of inflammation, we examined cellular and molecular mechanisms of kidney damage to determine whether selective activation of A 2A R will suppress inflammation in a rat model of glomerulonephritis. Activation of A 2A R reduced the degree of kidney injury in both the acute inflammatory phase and the progressive phase of glomerulonephritis. This protection against acute and chronic inflammation was associated with suppression of the glomerular expression of the MDC/CCL22 chemokine and down-regulation of MIP-1α/CCL3, RANTES/CCL5, MIP-1β/CCL4, and MCP-1/CCL2 chemokines. The expression of anti-inflammatory cytokines, IL-4 and IL-10, also increased. The mechanism for these antiinflammatory responses to the A 2A R agonist was suppression of macrophages function. A 2A R expression was increased in macrophages, macrophage-derived chemokines were reduced in response to the A 2A R agonist, and chemokines not expressed in macrophages did not respond to A 2A R activation. Thus, activation of the A 2A R on macrophages inhibits immune-associated inflammation. In glomerulonephritis, A 2A R activation modulates inflammation and tissue damage even in the progressive phase of glomerulonephritis. Accordingly, pharmacological activation of A 2A R could be developed into a novel treatment for glomerulonephritis and other macrophagerelated inflammatory diseases.

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“…HB-EGF has been implicated in the pathogenesis of glomerular injury of diverse etiologies, and increased glomerular HB-EGF expression has been reported in anti-Thy-1.1 mesangial proliferative glomerulonephritis (14,16), acute puromycin aminonucleoside nephrosis (15), passive Heymann nephritis (15), anti-glomerular basement membrane glomerulonephritis (18), and experimental focal glomerular sclerosis (17). A recent study also reported increased glomerular HB-EGF expression in human biopsy material taken from patients with glomerular diseases as diverse as lupus nephritis, membranoproliferative glomerulonephritis, IgA nephropathy, and Schönlein-Henoch purpura (16).…”

Section: Figmentioning

confidence: 99%

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

Robey¹,

Ma²,

Santos³

et al. 2002

Journal of Biological Chemistry

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Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogenactivated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (>10 nM) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the uniform requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury.

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Heparin-binding EGF-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats

Cited by 36 publications

References 67 publications

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Adenosine A_2Areceptor activation and macrophage‐mediated experimental glomerulonephritis

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

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Heparin-binding EGF-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats

Cited by 36 publications

References 67 publications

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Alterations of podocytes in a murine model of crescentic glomerulonephritis

Adenosine A2Areceptor activation and macrophage‐mediated experimental glomerulonephritis

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

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Adenosine A_2Areceptor activation and macrophage‐mediated experimental glomerulonephritis