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 altered proteoglycan deposition in the development of lung diseases. UDP-D-xylose: 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 lung tissue and in isolated fibroblasts, as well as the deposition of the proteoglycans versican, biglycan and decorin in rat lung tissue during bleomycin-induced lung injury. Rats were given, endotracheally, a single dose of bleomycin. Deposition of proteoglycans in lung tissue was assessed by immunohistochemistry and the catalytic activity of xylosyltransferase was determined with an acceptor peptide 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 in fibrotic regions in close proximity to alpha-smooth muscle actin-positive cells. In contrast, no changes in biglycan and decorin deposition in fibrotic lungs were observed, except for decorin in alveolar type II pneumocytes and alveolar macrophages. Bleomycin treatment of isolated rat lung fibroblasts resulted in a concentration-dependent increase of xylosyltransferase activity up to 2 mU bleomycin x mL(-1). The data suggest a participation of myofibroblasts with increased xylosyltransferase activities in accumulation of versican in fibrotic foci of injured lung tissue at the early stages of development of lung fibrosis.
Koslowski
R
R
Institutes of Physiological Chemistry, Dresden University of Technology, Germany.
Pfeil
U
U
Fehrenbach
H
H
Kasper
M
M
Skutelsky
E
E
Wenzel
K W
KW
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001706:Biopsy; D001761:Bleomycin / Q000009:adverse effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D007124:Immunoenzyme Techniques; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010430:Pentosyltransferases / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000097608:UDP Xylose-Protein Xylosyltransferase
D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D010430:Pentosyltransferases; D011509:Proteoglycans; D000097608:UDP Xylose-Protein Xylosyltransferase