We found that hgf was upregulated in the plasma ...

Limit such treatment as lung volume reduction surgery and lack of donor lungs for transplantation have to create new strategies for treatment of emphysema important global priority. True >> << Results showed that supplements of growth factor may improve the low level of exercise tolerance and gas exchange

associated with emphysema by inhibiting apoptosis of alveolar cell walls and increased alveolar regeneration

and angiogenesis in the pulmonary vessels. We found that HGF was upregulated in plasma and lung tissue in the acute phase after elastase induction. We thought that

these elevated levels of HGF were the result parakrinnoy mechanism in lung macrophages and endothelial cells and endocrine >> << mechanism in the liver and kidneys. Emphysema clinically characterized by local hypoxia, while some laboratory studies have shown that hypoxia

downregulates HGF gene expression in different cells. Thus, the endocrine system appeared to promote more preferably a transient increase of HGF compared with parakrinnoy system >> << In emphysema, whereas extrapulmonary HGF levels in this study. In our previous studies we have shown that

HGF acts as an important mitogen in the process of recovery from lung injury,

which was confirmed by current data, as shown in the

B. However, we also showed that disease progression was accompanied by a noticeable decrease in the production of HGF, possibly in response

to progressive hypoxia locally and in distant organs. In addition, decreased vascular reflects the severe loss of endothelial cells, which are sources of HGF, which leads

no stable accumulation of HGF and exhausted endogenous HGF, which may be associated with progressive destruction

lung parenchyma, connected commonly associated with loss of alveoli and blood vessels, by refusing tissue regeneration >>. << To test our hypothesis that the denial of sustainable endogenous HGF can lead to acute pulmonary pathophysiology,

human HGF transfection was in elastase treated rat model. Induction of expression of HGF was achieved, resulting in histological >> << and functional lung recoveries that were associated with regeneration of alveolar cells nearby. Interestingly, in

addition to the increase in human HGF, rat HGF concentration in lung tissue significantly increased in 5 - 8 times >> << compared to the nontreatment group. In this regard, in vitro studies have shown that exogenous human HGF significantly increases

rat endogenous HGF fibroblasts in culture, as well as endothelial cells (private communication with the SM and T. N). In addition, the same effects observed in vivo, as reported. Thus, we hypothesized that exogenous HGF added secretion and / or production of endogenous HGF in >> << autoinduction of HGF. This mode parakrinnoy HGF-mediated regeneration will produce favorable effects, locally limited to the lungs

with minimal side effects to other organs. Moreover, in addition to the assumption that transforming growth factor-b1 lasix and heart failure

(TGF-b1) participated in the arrest process of regeneration by inhibiting local production of HGF in hypoxic conditions,

HGF may inhibit TGF-b1 production and inhibit TGF-b1induced signal. Taken together, these results seem to indicate that HGF additives changes the failure of alveolar regeneration in the context

emphysema. Clearly, the functional impairment associated with emphysema occur in parallel with the degree of loss of light >> << vasculature. Furthermore, addition of secondary vasoconstriction, which occurs due to hypoxia leads to irreversible

progression towards pulmonary hypertension. Liebow

introduced vascular concept, which states that the reduction in blood supply to the small precapillary blood vessels >> << may contribute to the pathogenesis of emphysema. Interestingly, in the present study showed a significant increase in pulmonary vascular

elastase induced emphysema in rats following a request by HGF, whereas previous studies have shown that HGF

powerful causes angiogenesis in the heart, skin and lungs tissue. Despite the large number of factors were characterized angiogenesis remains to show whether other factors angiogenesis

such as basic fibroblast growth factor (FGF-b) and vascular endothelial growth factor (VEGF), may have a proliferative effect

in alveolar epithelial cells. In addition, unlike VEGF, which is induced and upregulated hypoxia and may lead to tissue edema

and would-FGF, which may contribute to fibrosis, HGF, seems to have no such side effects. Several lines of evidence have recently reported demonstrate that the process of programmed cell death, apoptosis, and is preceded by

progressive destruction of lung tissue in emphysema. In addition, elastase / antielastase imbalance manifests itself in disease may result from alveolar cell death, then inflammatory cells >> << invasion and violation of extracellular matrix. Hence, the conclusion that alveolar wall apoptosis suppressed HGF may provide a mechanical explanation

to prevent progressive tissue destruction in this model. Many studies have shown antyapoptotycheskoe

effects of HGF in different cell lines, while

it was also shown as septation caused a contributing factor in branching morphogenesis of the injured lung. Indeed, the development of alveolar septation in adults remains a serious problem in the development of adequate treatment for emphysema

. However, HGF may provide some biological effects in lung tissue after injury, including alveolar proliferation, angiogenesis,

tube formation and prevention of apoptosis. Taken together, we considered that HGF supplements can benefit lung >> << physiological functions in emphysema, minimizing the degree of lung damage and stimulates alveolar septation. In this study, HGF supplement was achieved by intravenous injection of the vector envelope HVJ,

, and the effect of one injection is provided by this method showed local storage for several months, which can be controlled by regulating

expression together gene from self-destruction. We believe it is important for use in therapeutic strategies to maintain a stable and long-term expression in addition to the continuing effects

HGF, especially chronic diseases such as emphysema. The method used in this study may be

perfect in this sense. Massaro and his colleagues conducted a study of pioneer skills retinoic acid to induce the formation of alveoli in rat model of emphysema. Administration

in HGF, which has both pulmotrophic and blood vessel activity, different from their method is that it is ideal as a resuscitation therapy

, considering the molecular pathogenesis of the disease, and is a reasonable strategy to carry out because of self-recovering

system inherent in man. To our knowledge, this is the first report to demonstrate the growth potential >> << factors in improving pulmonary emphysema pathophysiology in animal models. Future studies that use a combination of >> << growth factors and gene transfection technology goals and limited lung tissue may be useful to clarify the molecular mechanisms

for other lung diseases. More detailed studies are needed to determine a positive effect on

HGF on emphysema in clinical trials, we believe that the effect depends on the dose and the age and species. .

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