PDGF-BB induces expression of LTBP-1 but not TGF-beta1 in a rat cirrhotic fat storing cell line.
TGF-beta, a profibrogenic cytokine is predominantly secreted as a latent molecule complexed with one of the latent TGF-beta binding proteins (LTBP). Due to the proposed functions of LTBP-1 and -3 in regulating TGF-beta-bioavailability and -activity, we investigated the effects of PDGF-BB and TGF-beta1 on their expression levels in Cirrhotic fat storing cells (CFSC). CFSC basally express LTBP-1 and -3 and TGF-beta1. LTBP-1 colocalizes with LAP and the cells secrete some active TGF-beta1. Promoter studies showed no strong induction of the LTBP-1 promoters after stimulation, although mRNA and protein levels were increased by PDGF-BB treatment without affecting TGF-beta1 expression. Vice versa, TGF-beta1 treatment did not alter LTBP-1 expression while an autocrine induction was found. Our data indicate that LTBP-1 but not TGF-beta1 is induced by PDGF-BB and that TGF-beta1 autoinduction does not affect the expression of LTBP-beta1. This divergent regulation may represent an important mechanism for modulation of TGF-beta bioavailability.
Westhoff
Jens H
JH
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany.
Sawitza
Iris
I
Keski-Oja
Jorma
J
Gressner
Axel M
AM
Breitkopf
Katja
K
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000077214:Becaplermin; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008156:Luciferases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
D000925:Anticoagulants; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D008156:Luciferases