liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
Örebro University.
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
2012 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 318, no 5, 632-640 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2012. Vol. 318, no 5, 632-640 p.
Keyword [en]
Airway smooth muscle; Airway remodelling; Extracellular matrix; Hyaluronic acid; CD44; Focal adhesion kinase; Platelets
National Category
Basic Medicine
URN: urn:nbn:se:liu:diva-75382DOI: 10.1016/j.yexcr.2011.12.011ISI: 000300966300021PubMedID: 22227408OAI: diva2:506430
funding agencies|strategic areas Cardiovascular Inflammation Research Centre (CIRC)||Material in Medicine, the Heart- and Lung foundation||County of Ostergotlands Lan||STIFUD||Olle E||Swedish Research Council||Available from: 2012-02-28 Created: 2012-02-28 Last updated: 2012-04-03

Open Access in DiVA

fulltext(418 kB)459 downloads
File information
File name FULLTEXT01.pdfFile size 418 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Svensson Holm, Ann-CharlotteGrenegård, MagnusLindström, Eva G
By organisation
Experimental PathologyFaculty of Health SciencesPharmacology
In the same journal
Experimental Cell Research
Basic Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 459 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 91 hits
ReferencesLink to record
Permanent link

Direct link