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Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

Svensson Holm, Ann-Charlotte B. (författare)
Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Bengtsson, Torbjörn, 1955- (författare)
Örebro universitet,Institutionen för hälsovetenskap och medicin,Department of Biomedicine, Department of Biomedicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden,Örebro University
Grenegård, Magnus (författare)
Linköpings universitet,Farmakologi,Hälsouniversitetet,Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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Lindström, Eva G. (författare)
Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Lindström, Eva G (författare)
Linköpings universitet,Farmakologi,Hälsouniversitetet
Svensson Holm, Ann-Charlotte (författare)
Linköpings universitet,Experimentell patologi,Hälsouniversitetet
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San Diego, USA : Elsevier, 2012
Ingår i: Experimental Cell Research. - San Diego, USA : Elsevier. - 0014-4827 .- 1090-2422. ; 318:5, s. 632-640
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling. (C) 2011 Elsevier Inc. All rights reserved.


MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology (hsv//eng)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)


Airway smooth muscle
Airway remodelling
Extracellular matrix
Hyaluronic acid
Focal adhesion kinase
Airway smooth muscle; Airway remodelling; Extracellular matrix; Hyaluronic acid; CD44; Focal adhesion kinase; Platelets

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