Effects of decorin and biglycan on human airway smooth muscle cell proliferation and apoptosis

1 Meakins Christie Laboratories, McGill University, Montreal, Quebec; and 2 University of Montreal Hospital Center, Montreal, Quebec, Canada Submitted 19 October 2007 ; accepted in final form 30 January 2008 Proteoglycans (PG) are altered in the asthmatic airway wall. Because PGs are known to affect cell proliferation and apoptosis, we hypothesized that alterations in PG might influence the airway smooth muscle (ASM) hyperplasia observed in the asthmatic airway. Human ASM cells were seeded on plastic or plates coated with decorin (Dcn), biglycan (Bgn), or collagen type I (Col I) (1, 3, and 10 µg/ml). Cells were stimulated with platelet-derived growth factor (PDGF), and cell number was assessed at 0, 48, and 96 h. Cell proliferation was measured by bromodeoxyuridine (BrdU) incorporation and apoptosis by annexin V and propidium iodide staining at 48 h post-PDGF stimulation. A significant decrease in cell number was observed with cells seeded on Dcn (10 µg/ml) at 0, 48, and 96 h ( P < 0.01). Dcn induced both decreases in BrdU incorporation and increases in annexin V staining ( P < 0.05). Bgn decreased cell number at time 0 only ( P < 0.05) and affected neither proliferation nor apoptosis. Col I (10 µg/ml) caused a significant increase in cell number at 48 and 96 h ( P < 0.01). Adding exogenous Dcn (1–30 µg/ml) to the medium had no effect on cell number. Exposing Dcn-coated matrices to chondroitinase ABC, an enzyme that degrades glycosaminoglycan side chains, reversed the Dcn-induced decrease in cell number. These studies demonstrate that different PGs have variable effects on ASM cell proliferation and apoptosis. Recently described decreases in Dcn in the asthmatic airway wall could potentially permit more exuberant ASM growth. decorin; biglycan; collagen; asthma; airway remodeling Address for reprint requests and other correspondence: M. S. Ludwig, Meakins Christie Laboratories, 3626 St. Urbain St., Montreal QC Canada H2X 2P2 (e-mail: mara.ludwig{at}mcgill.ca )