Transforming growth factor-beta induces a chondroitin sulfate/dermatan sulfate proteoglycan in alveolar type II cells.
Alveolar type II cells can synthesize extracellular matrix (ECM) components in vitro, including proteoglycans. Transforming growth factor-beta (TGF-beta) profoundly influences ECM production and is found in areas of lung fibrosis. To determine whether type II cell proteoglycan synthesis is regulated by TGF-beta, we cultured adult rabbit type II cells with TGF-beta 1 and analyzed the synthesis of proteoglycans secreted into the culture medium. TGF-beta 1 increased 35SO4 incorporation into glycosaminoglycans of secreted proteoglycans 2.5-fold. Analysis of the intact proteoglycans revealed that TGF-beta 1 induced accumulation of a chondroitin sulfate/dermatan sulfate proteoglycan with molecular mass between 70 and 100 kDa and a core protein of 36 kDa. There were no effects on several other core proteins. Type II cells cultured with TGF-beta 1 and beta-D-xyloside, an acceptor for glycosaminoglycan polymerization, had increased glycosaminoglycan synthesis independent of the availability of core proteins. These data indicate that type II cell proteoglycan synthesis, at the levels of both core protein and glycosaminoglycans, is regulated by TGF-beta 1. We speculate that the induced 70- to 100 kDa proteoglycan is decorin, an ECM proteoglycan involved in collagen fibrillogenesis and TGF-beta binding.
Department of Pediatrics, Strong Children's Research Center, University of Rochester, New York 14642.
W M
WM
Maniscalco
M H
MH
Campbell
D000818:Animals; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006025:Glycosaminoglycans / Q000096:biosynthesis; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D013431:Sulfates / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D011509:Proteoglycans; D013431:Sulfates; D016212:Transforming Growth Factor beta; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates