Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD.
Glycosaminoglycans (GAG) are essential extracellular matrix molecules which regulate tissue flexibility, a parameter that is reduced in airways of patients with asthma and chronic obstructive pulmonary disease (COPD). We investigated the expression of GAG and their metabolising enzymes in primary human airway smooth muscle cells (ASMC) obtained from healthy donors (controls) and patients with asthma or COPD. Total GAG synthesis was assessed by [(3)H]-glucosamine incorporation. GAG were isolated, purified, fractionated by electrophoresis and characterised using specific GAG-degrading enzymes. Secretion of hyaluronic acid (HA) by ASMC from patients with asthma or COPD was significantly decreased compared with controls. RT-PCR analysis and western blotting revealed that this decrease was associated with a significant reduction in the expression of HA synthase-1 and -2 and a significant increase of hyaluronidase-1. Furthermore, the expression of the HA receptor CD44 was significantly decreased, whereas the receptor for HA-mediated motility was not expressed in asthma or COPD. Our results indicate that there is a decreased expression of HA in asthma and COPD associated with a synergistic regulation of HA metabolising enzymes that may regulate the pathological airway remodelling in these lung diseases.
Klagas
I
I
Dept Pharmacology, Aristotle University of Thessaloniki, Greece.
Goulet
S
S
Karakiulakis
G
G
Zhong
J
J
Baraket
M
M
Black
J L
JL
Papakonstantinou
E
E
Roth
M
M
D000328:Adult; D001249:Asthma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D005260:Female; D014453:Glucuronosyltransferase / Q000502:physiology; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000502:physiology; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase