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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver injuries induced by ischemia or physical trauma are characterized by noninflammatory damage frequently observed in a clinical setting. When the liver of rats was injured by ischemic treatment or physical crushing, necrotic tissue degeneration occurred in several sites of lobulus within 24 hr. Hepatocyte growth factor, a potent mitogen for adult rat hepatocytes in primary culture, was markedly induced in the livers of rats injured by ischemia or physical trauma. In both cases, the hepatocyte growth factor messenger RNA level in the injured liver reached about 10 to 20 times that of the normal level during 12 to 24 hr after liver injury. The increase in hepatocyte growth factor messenger RNA correlated well with the degree of liver damage as evaluated by serum ALT activity in the sera of rats. In situ hybridization showed that hepatocyte growth factor messenger RNA expression occurs in nonparenchymal liver cells, primarily in Kupffer cells of the ischemic liver. After the increase of hepatocyte growth factor messenger RNA in the injured liver, a marked compensatory hepatocyte DNA synthesis occurred 48 to 72 hr after these treatments. These results suggest that hepatocyte growth factor acts as a hepatotropic factor for liver regeneration after noninflammatory liver damage caused by ischemia and physical crush, probably through a paracrine mechanism.
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PMID:Rapid and marked induction of hepatocyte growth factor during liver regeneration after ischemic or crush injury. 128 Feb 46

Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration.
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PMID:Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions. 131 69

Renal tubular cells do not proliferate under normal intact conditions, whereas a marked regeneration is evident when tubular cells are injured by renal toxins or by ischemia. In case of compensatory renal growth too, hyperplasia of renal proximal tubular cells is observed. Various growth factors, including epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) seem to be involved in renal regeneration, however, the physiological role of these growth factors for the natural course of the renal regeneration have yet to be established. Hepatocyte growth factor (HGF), a potent mitogen for cultured renal tubular cells, may function as a renotropic factor, which enhances regeneration of the kidney. Once renal tubular cells are damaged by some agents, HGF mRNA, HGF activity and DNA synthesis of renal tubular cells are sequentially increased. Since both HGF mRMA and HGF protein are localized in renal interstitial cells, HGF seems to act on the tubular cells as a paracrine mediator. In addition to these results, HGF has multiple biological functions. This suggests that HGF possesses biological activities essential for renal regeneration.
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PMID:[Hypertrophy and hyperplasia of renal tubular interstitial cells--regulatory factors]. 756 25

Acute renal failure (ARF) is related to reversible tubular necrosis, usually caused by ischemia or toxic substances. Our knowledge of the pathophysiology of ARF stems from the study of animal models which reproduce either an ischemic or a toxic form of ARF. Classical studies using microdissection and micropuncture have characterized the salient mechanisms of ARF: vascular compromise with hypoperfusion and decrease in glomerular filtration rate, and tubular insult with cell necrosis and high intratubular pressure. More recent studies have emphasized the cellular and molecular events occurring during the course of ARF, including changes in cytoskeleton and matrix proteins, apoptosis and the role of Heat Shock Proteins. Endothelin and growth factors such as epidermal growth factor or hepatocyte growth factor seem to be important mediators in the regeneration phase of ARF. In various animal models, EGF, HGF or antagonists of endothelin receptors have a protective effect on renal function. These findings may be of clinical relevance, and suggest future therapeutic approaches in the treatment of ARF.
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PMID:[Experimental models of acute kidney failure]. 756 87

Hepatocyte growth factor (HGF) and its high-affinity receptor, c-met, have been found to increase in the whole kidney of the rat following several types of renal injury or renal hypertrophy. In an attempt to determine whether the upregulation of this growth factor and its receptor is selective for the regions of greatest anatomic change, and therefore likely to be important in regulating renal tubular hyperplasia and/or hypertrophy, we examined their expression in liver, whole kidney, and subsections of the kidney following either sham operation, transient ischemia of one kidney, or unilateral nephrectomy. The message for HGF was increased in both liver and kidney by all surgical procedures tested, including sham operation, and was seen predominantly in the outer cortex, the site of least morphological change. However, c-met was not upregulated by sham operation or in the liver, but rather was selectively upregulated only in the kidney in both the hypertrophy and hyperplasia (ischemia/reflow) models. Renal subsections revealed that this increase was confined to the renal medulla, with the greatest change in the outer medulla. Thus induction of the message for HGF can occur nonselectively and at sites distant to the injurious stimulus, whereas the target for HGF, c-met, is upregulated selectively at the site of greatest tubular injury or hypertrophy. These results support a role for HGF/c-met in regulation of these renal tubular events.
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PMID:Regional expression of hepatocyte growth factor/c-met in experimental renal hypertrophy and hyperplasia. 806 83

Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis of renal tubular cells after renal injuries caused by HgCl2 administration and unilateral nephrectomy and induced reconstruction of the normal renal tissue structure in vivo. Taken together with our previous finding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought renotropic factor for renal regeneration and may prove to be effective treatment for patients with renal dysfunction, especially that caused by cisplatin.
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PMID:Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. 818 13

Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes, possesses mitogenic and morphogenic activities for renal epithelial cells. To examine the renotropic function of HGF, we investigated the expression of HGF mRNA and HGF activity in the rat kidney after acute renal failure. When acute renal failure was induced by ischemia or by HgCl2 administration, a DNA synthesis occurred predominantly in the renal tubular cells located in the outer medulla with a peak at 48 h after the treatments. In both renal injuries, HGF mRNA in the kidney increased markedly, reaching a maximum 6 to 12 h after the treatments. HGF activity in the kidney also increased to three- to fourfold higher level than the normal level at 12 h after ischemic treatment or HgCl2 administration. In situ hybridization and immunohistochemical analysis indicated that both HGF mRNA and HGF protein were expressed in renal interstitial cells, presumably endothelial cells and macrophages, but not in tubular epithelial cells. In addition, HGF activity in the plasma of rats with renal ischemia or HgCl2 administration rapidly increased, reaching a maximum at 6 h after the treatment. One week after these injuries, HGF mRNA and HGF activity reverted to normal levels, and renal tubular cell regeneration ceased. Moreover, intravenous injection of human recombinant HGF into mice with acute renal failure caused by HgCl2 administration stimulated DNA synthesis of renal tubular cells in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acute renal injury. 834 15

Hepatocyte growth factor (HGF) is the most potent mitogen of mature hepatocytes in primary culture, and is a molecule composed of 69 kD alpha-chain and 34 kD beta-chain. HGF predominantly acts on various epithelial cells as a mitogen, motogen and a morphogen. HGF mRNA and HGF protein increases rapidly in the liver and plasma of rats with liver injury such as hepatitis, ischemia, physical crush and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells, sinusoidal endothelial cells, and Ito cells, but not in hepatocytes. HGF mRNA is also rapidly increased in the intact organs such as lung, kidney and spleen. Thus, HGF may act as a hepatotrophic factor for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, intravenously injected HGF enhances liver regeneration and protects hepatitis in vivo. Consequently, HGF may prove to be useful for the clinical treatment of patients with liver disease. Recently, we found a factor which specially appears in the blood of rats with organ injury and increases the synthesis of HGF, and it was named "injurin". IL-1 alpha and IL-1 beta are also positive regulators for the expression of the HGF gene, while TGF-beta and Dexamethazone down-regulate HGF expression.
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PMID:[Molecular biology of hepatocyte growth factor (HGF)]. 838 41

The mammalian kidney is susceptible to injury by ischemia/reperfusion and toxins, and regeneration after injury is characterized by hyperplasia and recovery of the damaged epithelial cells that line the tubules. Locally produced growth factors may serve as mediators of nephrogenesis and differentiation during renal development and of renal regeneration after acute injury. In cultured cells, administration of one or a mixture of growth factors to quiescent cells will initiate progression through the cell cycle and cell division. In the adult kidney, cell division normally is very low, but will increase up to 10-fold after acute injury. In addition to proliferation after lethal injury, there also is cellular repair in cells that have undergone sublethal injury. Recent studies indicate that growth factors inhibit programmed cell death in response to acute injury. Growth factors also may initiate or promote protein and lipid biosynthesis and provide an intracellular milieu that promotes cellular repair. In addition to cellular repair, growth factors also may be involved in the re-establishment of cell-extracellular matrix and cell-cell integrity. Finally, growth factors may limit injury by decreasing the factors that induce damage. Increased local renal expression of growth factors in response to acute injury include heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I), transforming growth factor-beta, parathyroid hormone-related peptide, and acidic fibroblast growth factor. In a number of experimental models of acute renal injury, administration of exogenous growth factors has been shown to accelerate both structural and functional recovery. Specifically, EGF, IGF-1, and HGF all have been shown to be effective in this regard. These studies are reviewed and potential therapeutic uses of growth factors and cytokines will be discussed.
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PMID:Growth factors and cytokines in acute renal failure. 911 40

Scatter factor (SF), also known as hepatocyte growth factor, is a potent mitogen that has been suggested to exhibit greater efficacy than vascular endothelial growth factor (VEGF) in rabbits with hindlimb ischemia. Our study examined the effects of SF on cardiovascular hemodynamics and compared the responses to VEGF. Hemodynamic parameters were monitored before and after administration of SF or VEGF in conscious, instrumented rats. Intravenous injection of SF produced a dose-related reduction in mean arterial pressure (MAP) and increase in heart rate (HR). These responses were significantly attenuated by pretreatment with N omega-nitro-L-arginine methyl ester a nitric oxide (NO) synthase inhibitor, suggesting the depressor effect of SF may be mediated by NO. SF (250 micrograms/kg) reduced stroke volume and cardiac output, but did not affect the maximal first derivation of left ventricular pressure (dP/dt), suggesting that the reduction in cardiac output is caused by decreased stroke volume that probably results from a reduction in venous return. Compared with SF, VEGF produced greater hypotensive and tachycardic responses and greater reductions in stroke volume and cardiac output, indicating that SF has fewer side effects on hemodynamics. Although both growth factors might reduce venous return, SF decreased hematocrit presumably through venodilation, whereas VEGF increased hematocrit as a result of vascular hyperpermeability.
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PMID:Hemodynamic effects of scatter factor in conscious rats. 930 Mar 11


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