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

Abstract

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 remodeling 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 plateletinduced 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.

CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

“…As a polysaccharide, HA has the potential to develop heparin‐induced thrombocytopenia, and an increased serum level of HA has been correlated with low platelets syndrome . It has been reported that CD44 is expressed on the surface of platelets, and it has previously been shown that platelets can bind to HA via surface‐expressed CD44 . Besides, CD44 is also expressed on circulating lymphocytes but does not bind to HA before receptor deglycosylation .…”

A structure-supporting, self-healing, and high permeating hydrogel bioink for establishment of diverse homogeneous tissue-like constructs

“…As the main components of the extracellular matrix, HA and proteins play an important role in tissue regeneration and repair. This biomimetic hydrogels has been used for research or application of brain [ 57 , 79 ], liver [ 80 ], muscle [ 81 , 82 ], skin [ 58 ] and cartilage [ 17 , 83 ] tissue engineering. Therefore, in addition to the permeability, HA and GEL in TSHSP bioink also contributed to the remarkable biological specificities of in vitro tissue-like constructs.…”

Hypoxia‐induced ARHGAP26 deficiency inhibits the proliferation and migration of human ductus arteriosus smooth muscle cell through activating RhoA‐ROCK‐PTEN pathway

“…2 In this study, downregulation of ARHGAP26 expression caused a decreased proliferation rate and ability of human DASMC to migrate, both of which are closely correlated with structural closure of human DA. HAS2, a key enzyme for HA production in mammalian cells and HA, which has been reported to be closely related to cell proliferation, adhesion, and migration, 19 were both reduced after downregulation of ARHGAP26 in human DASMCs in vitro. Yokoyama et al 20 pointed that when HA production was inhibited, the migration of DASMCs was negated.…”