Changes in xylosyltransferase activity and in proteoglycan deposition in bleomycin-induced lung injury in rat

Several lines of evidence support the hypothesis of the involvement of alte red proteoglycan deposition in the development of lung diseases. UDP-D-Xylo se: core protein beta -D-xylosyltransferase (UDP-xylosyltransferase; EC 2.4 .2.26) is a key enzyme for the glycosylation of proteoglycan core proteins. This study examined the catalytic activity of UDP-xylosyltransferase in lu ng tissue and in isolated fibroblasts, as well as the deposition of the pro teoglycans versican, biglycan and decorin in rat lung tissue during bleomyc in-induced lung injury. Rats were given, endotracheally, a single dose of bleomycin. Deposition of proteoglycans in lung tissue was assessed by immunohistochemistry and the c atalytic activity of xylosyltransferase was determined with an acceptor pep tide of the sequence Q-E-E-E-G-S-G-G-G-Q-G-G as a substrate. The results show coincidence of increasing xylosyltransferase activities in lung tissue with accumulation of versican at alveolar entrance rings and i n fibrotic regions in close proximity to alpha -smooth muscle actin-positiv e cells. In contrast, no changes in biglycan and decorin deposition in fibr otic lungs were observed, except for decorin in alveolar type II pneumocyte s and alveolar macrophages. Bleomycin treatment of isolated rat lung fibrob lasts resulted in a concentration-dependent increase of xylosyltransferase activity up to 2 mU bleomycin(.)mL(-1). The data suggest a participation of myofibroblasts with increased xylosyltr ansferase activities in accumulation of versican in fibrotic foci of injure d lung tissue at the early stages of development of lung fibrosis.