Hepatocyte growth factor (HGF) mediates the sustained formation of 1,2‐diacylglycerol via phosphatidylcholine—phospholipase C in cultured rat hepatocytes

Osada, Shinji; Saji, Shigetoyo; Nakamura, Toshikazu; Nozawa, Yoshinori

doi:10.1016/0014-5793(92)80554-t

Cited by 52 publications

(23 citation statements)

References 32 publications

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“…7). These findings are consistent with an earlier report that HGF/SF increases the concentration of intracellular diacylglycerol, an essential cofactor for protein kinase C, through a phospholipase C-dependent pathway (63). Interestingly, collagen induction of collagenase-1 expression is also both tyrosine kinase-and protein kinase C-dependent (21).…”

Section: Discussionsupporting

confidence: 82%

Mechanisms of Hepatocyte Growth Factor Stimulation of Keratinocyte Metalloproteinase Production

Dunsmore¹,

Rubin

Kovacs³

et al. 1996

Journal of Biological Chemistry

105

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Matrix metalloproteinases participate in normal physiologic processes; however, their overproduction has been associated with connective tissue destruction in a variety of pathological states. Migrating basal keratinocytes transiently express collagenase-1 during normal cutaneous reepithelialization. However, the overexpression of both collagenase-1 and stromelysin-1 has been associated with the pathogenesis of chronic nonhealing ulcers. Aberrant expression of metalloproteinases in inflammation is mediated, at least in part, by soluble factors. Since hepatocyte growth factor/scatter factor (HGF/SF) has been reported to promote keratinocyte migration and proliferation, key events in wound repair, and since HGF/SF is produced by dermal fibroblasts and its c-Met receptor is expressed by basal keratinocytes in wounded skin, we have studied the effects of HGF/SF upon keratinocyte metalloproteinase expression. We have found that HGF/SF can stimulate keratinocyte collagenase-1 and stromelysin-1 production in a dose-dependent and matrix-dependent manner. Expression of 92-kDa gelatinase was not affected by HGF/SF. We determined that HGF/SF regulation of collagenase-1 expression is transcriptionally mediated and requires tyrosine kinase and protein kinase C activaties. HGF/ NK1, a naturally occurring, truncated form of HGF/SF, also stimulates collagenase-1 production, but much less efficiently than does the parent molecule. However, HGF/NK2, another HGF/SF splice variant, as well as heparin, potently inhibit HGF/SF-induced collagenase-1 synthesis. These results indicate that HGF/SF and its naturally occurring splice variants have diverse biological effects on keratinocytes and suggest an additional mechanism whereby HGF/SF may regulate keratinocyte function during wound repair.Matrix metalloproteinases are a gene family of zinc-dependent enzymes with the collective capacity to degrade virtually all extracellular matrix components (1). At present, the matrix metalloproteinase gene family consists of three interstitial collagenases (2-4), three stromelysins (5-7), two gelatinases (8, 9), matrilysin (10), metalloelastase (11, 12), and two membrane-type metalloproteinases (13,14). With the notable exception of matrilysin (15, 16), matrix metalloproteinases are not constitutively expressed in normal tissues. Their expression is induced, however, in a variety of physiologic and pathologic conditions, including cutaneous wound repair.Collagenase-1 (MMP-1) 1 and stromelysin-1 (MMP-3) are two matrix metalloproteinases produced by keratinocytes in response to skin injury (17,18,22). These enzymes exhibit distinct substrate specificities and spatial localization within a wound. Collagenase-1 is capable of degrading fibrillar collagens (types I and III), abundant constituents of the dermal matrix, whereas stromelysin-1 degrades basement membrane components such as laminin and proteoglycans. Collagenase-1 is invariably produced by the migrating front of basal keratinocytes in both acute and chronic wounds (17)(18)(19)(20) and is marke...

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Section: Discussionsupporting

confidence: 82%

Mechanisms of Hepatocyte Growth Factor Stimulation of Keratinocyte Metalloproteinase Production

Dunsmore¹,

Rubin

Kovacs³

et al. 1996

Journal of Biological Chemistry

105

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“…The mechanisms through which HGF-induced calcium entry occurs are still controversial. The activation of c-MET by HGF causes the sustained formation of DAG and inositol 1,4,5 triphosphate (IP 3 ) by PLC [25]. These observations fit well with TRPC6 mediating the HGF-induced inflow of extracellular Ca 2+ .…”

Section: Discussionsupporting

confidence: 70%

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Wang¹,

Yue²,

Li³

et al. 2010

Asian J Androl

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Hepatocyte growth factor (HGF) is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 (TRPC6) channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques (whole-cell patch clamp configuration) and Ca 2+ imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-like currents evoked by oleoyl-2-acetyl-sn-glycerol (OAG). Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG-and HGF-induced Ca 2+ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.

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“…These findings are reminiscent of a previous report that HGF increases the concentration of intracellular diacylglycerol, an essential cofactor for PKC, through a phospholipase C-dependent pathway in cultured rat hepatocytes. 28 The specific PKC isoform involved in this process remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

et al. 2007

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B ile acids are physiological detergents that facilitate absorption, transport, and distribution of sterols and lipid-soluble vitamins and disposal of toxic metabolites and xenobiotics. Bile acid synthesis and cholesterol 7␣-hydroxylase (CYP7A1) 2 gene transcription are inhibited by bile acids returning to the liver via enterohepatic circulation of bile acids. 1 Because bile acids are amphipathic molecules that function as powerful detergents, their concentrations in hepatocytes have to be tightly regulated to prevent cell damage. 2 Bile acids are also signaling molecules that activate nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor, and vitamin D3 receptor and play important roles in the regulation of bile acid synthesis, cholesterol metabolism, and drug metabolism. 2 It has been reported that bile acid synthesis and CYP7A1 activity are suppressed after partial hepatectomy and during liver regeneration in animals and human patients. [3][4][5] The increase of bile acids in the remaining hepatocytes after partial hepatectomy and in the early stage of liver regeneration and injury inhibits bile acid synthesis and increases bile acid excretion to protect the liver from accumulating toxic bile acids. A recent study showed that bile acids and FXR are involved in liver regeneration in mice, as FXR-null mice had a lower rate of liver regeneration. 6 However, the molecular mechanism underlying the bile acid effect on liver regeneration remains unclear. Abbreviations: CBP, cAMP response element binding protein

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Hepatocyte growth factor (HGF) mediates the sustained formation of 1,2‐diacylglycerol via phosphatidylcholine—phospholipase C in cultured rat hepatocytes

Cited by 52 publications

References 32 publications

Mechanisms of Hepatocyte Growth Factor Stimulation of Keratinocyte Metalloproteinase Production

Mechanisms of Hepatocyte Growth Factor Stimulation of Keratinocyte Metalloproteinase Production

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

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