Hepatocyte growth factor stimulates phosphoinositide hydrolysis and mitogenesis in cultured renal epithelial cells

Harris, Raymond C.; Burns, Kevin D.; Alattar, Maha; Homma, Teiichi; Nakamura, Toshikazu

doi:10.1016/0024-3205(93)90430-b

Cited by 28 publications

(15 citation statements)

References 31 publications

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“…38,39 Production of HGF in intrinsic glomerular cells (eg, mesangial cells) might increase. 40 Enhanced procoagulant activity in glomerulonephritis can lead to an increase in thrombin. 41 Finally, accumulation of basement membrane and interstitial collagens is often evident in glomerulopathies.…”

Section: 13mentioning

confidence: 99%

Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation

Cybulsky

McTavish

Papillon

et al. 1999

The American Journal of Pathology

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Section: 13mentioning

confidence: 99%

Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation

Cybulsky

McTavish

Papillon

et al. 1999

The American Journal of Pathology

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“…HGF/SF exerts powerful mitogenic effects on epithelial cells, including renal proximal tubule cells (Harris et al, 1993), having been shown in mice to prevent the onset of renal dysfunction and to stimulate DNA synthesis of renal tubular cells (renal regeneration) after injury (Kawaida et al, 1994). Serum levels of HGF/SF are rapidly induced after renal injury or failure (Chang et al, 1996).…”

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confidence: 99%

“…Serum levels of HGF/SF are rapidly induced after renal injury or failure (Chang et al, 1996). HGF/SF is also believed to have a role in normal renal development and is the most potent renal tubular cell mitogen identified so far (Harris et al, 1993;Cantley et al, 1994;Woolf et al, 1995). Precise details of how HGF/SF promotes renal tubular cell mitogenesis are not known, although HGF/SF stimulation has been reported to increase in vivo expression of the VEGF gene in non-renal systems (Silvagno et al, 1995).…”

mentioning

confidence: 99%

Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related genes

Clifford

Czapla²,

Richards³

et al. 1998

Br J Cancer

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Hepatocyte growth factor (HGF/SF) is a potent renal proximal tubular cell (PTEC) mitogen involved in renal development. HGF/SF is the functional ligand for the c-met proto-oncogene, and germline c-met mutations are associated with familial papillary renal cell carcinoma. Somatic von Hippel-Lindau disease tumour-suppressor gene (VHL) mutations are frequently detected in sporadic clear cell renal cell carcinomas (RCC), and germline VHL mutations are the commonest cause of familial clear cell RCC. pVHL binds to the positive regulatory components of the trimeric elongin (SIII) complex (elongins B and C) and has been observed to deregulate expression of the vascular endothelial growth factor (VEGF) gene. HGF/SF has similarly been reported to up-regulate expression of the VEGF gene in non-renal experimental systems. To investigate the mechanism of HGF/SF action in PTECs and, specifically, to examine potential interactions between the HGF/c-met and the VHL-mediated pathways for renal tubular growth control, we have isolated untransformed PTECs from normal kidneys, developed conditions for their culture in vitro and used these cells to investigate changes in mRNA levels of the VHL, elongin A, B and C, VEGF, c-myc, c-fos and c-met genes after HGF/SF exposure. Significant elevations in the mRNA levels of VEGF, c-myc, c-fos, c-met and elongins A, B and C, but not VHL, were detected after HGF/SF stimulation of human PTECs (P < 0.02), with a consistent order of peak levels observed over successive replicates (c-fos at 1 h, VEGF at 2-4 h, c-myc, at 4 h, followed by c-met and all three elongin subunits at 8 h). This study highlights the spectrum of changes in gene expression observed in PTECs after HGF/SF stimulation and has identified possible candidate mediators of the HGF/SF-induced mitogenic response. Our evidence would suggest that the changes in PTEC VEGF expression induced by HGF/SF are mediated by a VHL-independent pathway. Images Figure 1

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Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expressions of c-jun and c-fos: Involvement of protein tyrosine kinase, protein kinase C, and Ca2+

et al. 1996

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Hepatocyte growth factor (HGF) exerts several distinct efHepatocyte growth factor (HGF) activated phospholifects on a variety of cell types: it is the most potent mitogen pase D (PLD) in primary-cultured rat hepatocytes, as for hepatocytes in primary culture as well as other cell assessed by the formation of phosphatidylbutanol types, [1][2][3][4][5] it is a motility and invasion-inducing factor for epi-(PBut), a specific and stable product of PLD activity in thelial and endothelial cells, 6-9 it has cytotoxic and cytostatic the presence of 0.3% butanol. PLD hydrolyzes phosphatieffects on some cell lines, 10-12 and it is an inducer of epithelial dylcholine to choline and phosphatidic acid (PA), which morphogenesis. 13,14 The HGF receptor is the c-met protooncois further metabolized to diacylglycerol (DG) by PA gene product 15,16 and several signaling events have been rephosphohydrolase (PAP). In HGF-stimulated hepatoported following HGF receptor activation. [17][18][19][20][21][22][23] In the previous cytes, butanol prevented the formation of PA and DG.reports, 19,23 we showed that HGF stimulated inisitol 1,4,5-A PAP inhibitor, propranolol, inhibited DG production trisphosphate formation and increased in intracellular Ca 2/ with a reciprocal increase of PA, implying that PLD concentration. In contrast to rapid and transient change of played a role in the formation of not only PA but DG.trisphosphate, 1,2-diacylglycerol (DG) formation was biphaInhibitors for protein kinase C (PKC), Ro31-8425, H-7, sic and the second sustained phase was mainly caused by and calphostin C, reduced HGF-induced PLD activation.phosphatidylcholine ( PA can be further converted to DG by PA phosphohydrolase analog, oleylacetylglycerol (OAG), activated the expres-(PAP). Moreover, it has recently been reported that vasopression of c-jun and c-fos messenger RNAs (mRNAs). Ro31-sin, phorbol myristate acetate (PMA), or A23187 activated 8425, calphostin C, and genistein, which prevented PLD in rat hepatocytes, 27 and that PLD activity in hepato-HGF-induced PLD activation, inhibited induction of cytes appeared to be mediated by protein kinase C (PKC)-these immediate early genes. Butanol and propranolol dependent and Ca 2/ -dependent pathways. Furthermore, at concentrations which effectively inhibited the forma-PLD in rat liver plasma membrane is activated by a small G tion of DG, suppressed HGF-induced expression of c-jun protein, RhoA. 28 However, little information is available and c-fos mRNAs. However, HGF-induced mitogen-actiabout PLD in the HGF-mediated signaling pathway in hepavated protein kinase (MAPK) activation was not affected tocytes. by both butanol and propranolol. These results suggestIn the present study, we have examined the PLD activation that PTK, PKC, and Ca 2/ regulate HGF-induced PLD acin HGF-stimulated rat hepatocytes in primary culture. The tivation, and that DG produced by PLD pathway may results suggest that PKC and extracellular Ca 2/ play implay a role in the induction of immediate early genes, portant roles in HGF-sti...

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Hepatocyte growth factor stimulates phosphoinositide hydrolysis and mitogenesis in cultured renal epithelial cells

Cited by 28 publications

References 31 publications

Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation

Role of Extracellular Matrix and Ras in Regulation of Glomerular Epithelial Cell Proliferation

Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related genes

Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expressions of c-jun and c-fos: Involvement of protein tyrosine kinase, protein kinase C, and Ca2+

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