| 1. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Autocrine production of biologically active hepatocyte growth factor (HGF) by injured human skin
- 2006
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Ingår i: Journal of dermatological science (Amsterdam). - : Elsevier BV. - 0923-1811 .- 1873-569X. ; 43:1, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHepatocyte growth factor (HGF) is a potent regenerative factor involved in wound healing. Previous studies have shown that mesenchymal cells produce HGF, stimulating epithelial cells in a paracrine fashion.ObjectiveTo examine whether autocrine HGF production by keratinocytes can occur upon skin injury.MethodsA 31-year-old male patient sustained a burn affecting 80% of his total body surface area. Biopsies were taken from intact skin near the injured area, and skin keratinocytes were separated and cultured. Conditioned medium from keratinocytes was analyzed for HGF by ELISA, surface plasmon resonance (SPR), and dot blotting. Binding of HGF from conditioned medium to its receptor, c-Met, was compared with recombinant HGF by SPR. Finally, we examined the motogenic effect on mouse transformed skin epithelial cells (CCL-53.1) of HGF from conditioned medium.ResultsHGF was detected in the cultured keratinocyte medium. Similar to recombinant HGF, HGF from conditioned medium had a high affinity for dextran sulfate and albumin, and the same epitopes were engaged by the interaction of HGF with the c-Met receptor. The conditioned medium from keratinocytes obtained from the burn patient, but not medium from keratinocytes obtained from healthy volunteers, accelerated the motogenesis of CCL-53.1 cells. Unexpectedly, anti-HGF antibodies did not prevent this effect. However, anti-c-Met antibodies completely inhibited the motogenic effect.ConclusionUpon injury, human skin keratinocytes might produce biologically active HGF in an autocrine fashion. This HGF might have different structural and/or biological properties from HGF produced by mesenchymal cells.
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| 2. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor
- 2008
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 26:3, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity.
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| 3. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Hepatocyte growth factor (HGF) in fecal samples : rapid detection by surface plasmon resonance
- 2005
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 5:13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.MethodWe utilised SPR to detect hepatocyte growth factor (HGF) in reconstituted faecal samples and studied samples from patients with infectious gastroenteritis (n = 20) and normal controls (n = 10). Mouse anti-human HGF monoclonal antibodies and recombinant human HGF receptor (c-Met)/Fc chimera were immobilised in flow cells of a CM5 biosensor chip.ResultsWe found that infectious gastroenteritis produced a higher signal response compared to controls, due to binding of HGF to monoclonal anti-HGF antibody as well as binding of HGF to c-Met receptor (p < 0.01). The SPR signal response correlated with results from ELISA (r = 72%, p > 0.001). The signal response decreased significantly (p < 0.05) when samples were diluted with dextran, because of reduction in both specific as well as unspecific binding of HGF to dextran. The decrease in the specific response might imply that the dextran- binding site for HGF overlaps with the antibody binding epitope, or that dextran binding induces a conformational change of the HGF molecule. Bands corresponding to HGF were found by gel electrophoresis of purified faeces in an affinity chromatography column immobilised by HGF ligands.ConclusionDetermination of HGF by SPR might be beneficial in diagnosis of acute situations that present with symptoms of gastroenteritis and may, possibly, guide appropriate medical treatments. This is to our knowledge the first report on the use of SPR for detection of HGF in faeces samples.
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| 4. |
- Abednazari, Hossein, 1959-, et al.
(författare)
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Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia
- 2006
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Ingår i: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 52:5, s. 260-263
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Tidskriftsartikel (refereegranskat)abstract
- Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).
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| 5. |
- Ljunggren, Stefan, 1988-, et al.
(författare)
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Modified lipoproteins in periodontitis : a link to cardiovascular disease?
- 2019
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Ingår i: Bioscience Reports. - : Portland Press. - 0144-8463 .- 1573-4935. ; 39:3
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Tidskriftsartikel (refereegranskat)abstract
- There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesize that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, this study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient-ultracentrifugation. Proteins were separated by two-dimensional gel-electrophoresis and identified by map-matching or by nano-liquid chromatography followed by mass spectrometry. ApoA-I methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed.Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in HDL from the patients. In LDL/VLDL, the levels of apoL-1 and platelet-activating factor acetylhydrolase as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. Alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2.Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as posttranslational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).
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| 6. |
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| 7. |
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| 8. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia
- 2002
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 96:2, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.
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| 9. |
- Nayeri, Fariba, 1958-
(författare)
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Hepatocyte growth factor : Studies on local and systemic release and effects during infectious disease; in vivo and in vitro
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interaction of mesenchymal and epithelial cells that occurs after organ injuries results in enhanced production of cytokines, such as hepatocyte growth factor (HGF). HGF is a glycoprotein with unique properties that contribute to wound healing after injuries. In the present thesis, the release and role of HGF during infectious diseases have been investigated with particular emphasis on pneumonia and meningitis. First, a standard method for serum handling of HGF was determined. It was shown that HGF was stable in the serum after separation and several freeze-thaw cycles, keeping at room temperature for several hours or storage at -70 °C for several months, shaking or adding heparin and albumin did not affect HGF levels in serum. However, for reliable results whole blood had to be separated within one hour after venipuncture at room temperature or kept at 4-8 °C in the case of longer storage before separation. Following this standard method, the concentration of HGF during infectious diseases was studied. In another study we had previously shown that levels of HGF in serum increased during the acute phase of several infectious diseases. In this thesis a simultaneous enhanced production of HGF locally at the site of injury was studied. It was shown that concentration of HGF increased locally in cerebrospinal fluid during meningitis. Levels of HGF were significantly higher during bacterial meningitis than viral meningitis and concentration of HGF in cerebrospinal fluid might be used as a tool in diagnosis of bacterial meningitis. It was shown an enhanced local production of HGF in exhaled breath condensate in pneumonia that did not decrease significantly after 4 weeks in spite of the fact that the patient had recovered clinically and in the X-ray controls. This might show a long repair and healing process after pneumonia. Serum levels of HGF were significantly higher in pneumonia caused by Streptococcus pneumoniae than in other causes of pneumonia. In pneumonia, serum levels ofHGF decreased within 48 hours after efficient antibiotic therapy was started and normalized at convalescence. However, the levels of HGF in serum increased when treatment was ineffective and no clinical improvement was observed. When the appropriate therapy was initiated, the levels of HGF decreased followed by clinical recovery. Serum levels of HGF were able to predict therapy results at least as reliably as CRP within 48 hours after treatment. Thus HGF was shown to be a diagnostic moment for acute bacterial infections, and following levels of HGF in serum may perhaps be used as a prognostic marker in the course of treatment of infectious diseases such as pneumonia. The physiological effects of HGF on chronic leg ulcers(> 1 år) in 11 elderly patients were studied and an enhanced microcirculation that was significantly correlated to the healing percentage was observed after local HGF treatment. The infected ulcers that received a combined treatment of HGF and appropriate antibiotic responded with a high percentage of healing in three patients with chronic leg ulcers that had not responded to other treatments (including antibiotics) previously. The effect of HGF on injured mouse melanoma cell monolayer was investigated in vitro and showed that HGF caused migration of neighbouring cells towards the nude injured area in a dose-dependent manner. Concomitant morphogenic effects were observed. The actin structure in the cytoskeleton was changed by HGF treatment as studied by confocal microscopy. According to these results it could be cocluded that injuries caused by infectious organisms enhance the local and systemic production of HGF. This might be beneficial in healing of damage after such injuries. Determination of natural HGF in serum might be used as a diagnostic and prognostic marker during infectious diseases. Exogenous administration of recombinant HGF could be a beneficial treatment for injuries such as chronic leg ulcers particularly combined with the appropriate antibiotic in the case of obvious infection.
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| 10. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Hepatocyte growth factor, expression, concentration and biological activity in chronic leg ulcers
- 2005
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Ingår i: Journal of dermatological science (Amsterdam). - : Elsevier BV. - 0923-1811 .- 1873-569X. ; 37:2, s. 75-85
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Tidskriftsartikel (refereegranskat)abstract
- Background:Hepatocyte growth factor (HGF) is a multifunctional cytokine that is involved in recovery process after organ injuries.Objective:We studied HGF and the membrane bound receptor, c-met locally in patients who suffered from chronic leg ulcers (≥1 year) caused by venous insufficiency.Methods:Skin biopsies from the edge of the ulcers were taken from patients (n = 13) and studied by immunohistochemical staining for detection of HGF and c-met. Skin biopsies from healthy volunteers (n = 10) were used as the control material. Ulcer secretion from chronic ulcers (n = 11) was examined for the presence of HGF by ELISA and the concentration of HGF was compared with acute ulcers in healthy controls (n = 10) and in patients operated for a non-invasive breast cancer (n = 12).Results:We observed that c-met expression in the ulcer area increased significantly in chronic ulcers compared to controls (p = 0.005). Concentration of ulcer-HGF in the patients with chronic ulcer was significantly higher than acute ulcers (p < 0.01). The biological activity of HGF in ulcer secret was assessed in-vitro in transferred, mouse skin epithelial cell monolayer. Enhanced migration and morphologic changes were seen after adding ulcer secret from acute ulcers (>1 ng/mL) that was inhibited by anti-HGF antibodies. No biological activity was observed by adding ulcer secret from chronic ulcers irrespective HGF concentration.Conclusion:We conclude that in chronic skin ulcers decreased biological activity of endogenous HGF and overexpression of c-met is seen which might explain fibrosis and delayed recovery. Administration of exogenous active HGF might contribute to accelerated healing in these patients.
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