Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF.
In normal liver, lipocytes are the principal reservoir for retinoids, which are stored as retinyl esters. In liver injury, lipocytes activate into myofibroblast-like cells, which lack retinoid. We examined mechanisms of retinoid loss using a culture model in which lipocyte activation is provoked by exposure to Kupffer cell-conditioned medium (KCM) (S.L. Friedman and M. J. P. Arthur, J. Clin. Invest. 84: 1780-1785, 1989). In lipocytes exposed to KCM, there was approximately 11-fold more retinol in medium than in untreated cells, without release of retinyl esters. Both bile salt-dependent and -independent retinyl ester hydrolase was entirely intracellular, suggesting that the increase in retinol was due to intracellular hydrolysis; activity of bile salt-independent hydrolase was increased in KCM-treated lipocytes. Release of retinol was serum dependent and inhibited 40% by antibodies to platelet-derived growth factor (PDGF). The addition of 10 nM PDGF to serum-free KCM also induced retinol release. Lipocyte expression of mRNAs for cellular retinol-binding protein, retinoic acid receptor (RAR)-alpha, and RAR-beta was unchanged after exposure to KCM. In summary, activation of cultured lipocytes by KCM is accompanied by serum- and PDGF-dependent release of retinol; a similar mechanism may underlie retinoid loss by activated lipocytes in vivo.
Liver Core Center, San Francisco General Hospital, California.
S L
SL
Friedman
S
S
Wei
W S
WS
Blaner
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D015152:Blotting, Northern; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D007700:Kinetics; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism*
D001647:Bile Acids and Salts; D017077:Culture Media, Conditioned; D010169:Palmitic Acids; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D019308:Palmitic Acid; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase