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High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. PEAS Institute, Linköping, Sweden.
PEAS Institute, Linköping, Sweden.
Department of Nephrology UHL, County Council of Östergötland, Linköping, Sweden; Department of Medicine and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
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2012 (English)In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 3, no 4, p. 516-523Article in journal (Refereed) Published
Abstract [en]

Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased affinity to HSPG (P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

Place, publisher, year, edition, pages
Irvine, USA: Scientific Research Publishing, 2012. Vol. 3, no 4, p. 516-523
Keywords [en]
Chronic Renal Failure, Hepatocyte Growth Factor, Biological Activity, Neutrophils
National Category
Medical and Health Sciences Medical Bioscience
Research subject
Biomedicine; Medicine
Identifiers
URN: urn:nbn:se:oru:diva-25337DOI: 10.4236/abb.2012.324068OAI: oai:DiVA.org:oru-25337DiVA, id: diva2:547061
Note

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Available from: 2012-08-27 Created: 2012-08-27 Last updated: 2018-08-28Bibliographically approved
In thesis
1. The role of peridontitis and hepatocyte growth factor in systemic inflammation
Open this publication in new window or tab >>The role of peridontitis and hepatocyte growth factor in systemic inflammation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

An essential goal in addressing inflammation is the return of tissue to homeostasis. Persistent infections often cause prolonged response and accumulation of immune cells, inducing imbalance in pro- and anti-inflammatory mediators, tissue destruction, and chronic inflammation. In periodontal disease, bacteria of the dental plaque are the primary aetiologic agents. Coronary artery disease (CAD) and chronic renal failure (CRF) are associated with periodontitis and involve systemic inflammation with atherosclerotic and fibrotic processes. The aims of this thesis were to study the effect of the bacterium Porphyromonas gingivalis and the anti-inflammatory mediator lipoxin A4 (LXA4) on blood cells in vitro, as well as to measure the expression of hepatocyte growth factor (HGF) in patients with periodontitis, CAD, and CRF. We found that LXA4 inhibits P. gingivalis–induced leukocyte platelet aggregation and reactive oxygen species (ROS) production in whole blood, by antagonizing the upregulation of CD11b/CD18 on leukocytes. The serum concentration of HGF was elevated in patients with periodontitis, CAD and CRF, indicating a systemic inflammation. However, the biological activity of HGF was reduced in serum from CRF patients and in saliva and gingival crevicular fluid of patients with periodontitis. This finding correlated with reduced growth of gingival epithelial cells incubated with saliva from patients with periodontitis. Neutrophil proteases reduced the biological activity of HGF in patients with CRF, and HGF expression in patients with periodontitis was associated with higher concentration and numbers of species of periodontal bacteria. In conclusion, these studies suggest that systemic spreading of periodontal bacteria, leukocyte-platelet activation and disturbed HGF-expression are crucial components involved in tissue degradation and progression of chronic inflammation.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 86
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 83
Keywords
Hepatocyte growth factor, Porphyromonas gingivalis, periodontitis, systemic inflammation, coronary artery disease, chronic renal failure, lipoxin
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-28541 (URN)978-91-7668-922-6 (ISBN)
Public defence
2013-05-08, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2017-10-17Bibliographically approved

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Lönn, JohannaBengtsson, Torbjörn

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