TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression.
Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF-beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved.
Haberstroh
U
U
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Zahner
G
G
Disser
M
M
Thaiss
F
F
Wolf
G
G
Stahl
R A
RA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology*; D007074:Immunoglobulin G / Q000276:immunology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007074:Immunoglobulin G; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor