Cadmium inhibits proteoglycan and procollagen production by cultured human lung fibroblasts

Chronic inhalation of cadmium at the workplace or in cigarette smoke is associated with emphysema, a disease characterized by extensive disruption of lung connective tissue. We have previously shown that cadmium, at noncytotoxic doses, inhibits fibroblast procollagen production in vitro, with maximal inhibitory effects of 69 +/- 6% (P < 0.01) at 30 µM cadmium chloride (CdCl2). In this paper we show that at similar doses, cadmium also inhibits proteoglycan synthesis, with values reduced by between 36 +/- 4% (P < 0.01) and 42 +/- 6% (P < 0.01) for proteoglycans secreted into the culture media and associated with the cell layer, respectively. The greatest inhibition was obtained for the major matrix-associated proteoglycans, versican, decorin, and the large heparan sulfate proteoglycans, with synthesis values reduced by between 60 and 70%. Biglycan and other heparan sulfate proteoglycans were also affected, with synthesis values reduced by between 25 and 45%. In contrast, total protein synthesis was unaffected. Furthermore, effects of cadmium at the protein level were mirrored by reduction in messenger RNA levels for alpha1(I) procollagen, versican, and decorin. These data support the hypothesis that cadmium may play an important role in the pathogenesis of emphysema associated with chronic inhalation of cadmium fumes by inhibiting the production of connective tissue proteins.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
Administration, Inhalation
Cadmium
Cells, Cultured
Chondroitin Sulfate Proteoglycans
Chondroitin Sulfates
Decorin
Dermatan Sulfate
Disaccharides
Emphysema
Extracellular Matrix Proteins
Humans
Lectins, C-Type
Lung
Procollagen
Protein Synthesis Inhibitors
Proteoglycans
RNA, Messenger
Versicans
Journal Article
Research Support, Non-U.S. Gov't

Laurent, G J (författare)
Westergren-Thorsson, GLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-gwt (författare)
University College LondonInstitutionen för experimentell medicinsk vetenskap (creator_code:org_t)

Ingår i:American Journal of Respiratory Cell and Molecular Biology: American Thoracic Society19:3, s. 498-5061044-15491535-4989

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