Inhibitory effect of cepharanthine on fibronectin production in growth factor-stimulated rat mesangial cells.
We examined the effect of cepharanthine, a biscoclaurine alkaloid, on extracellular matrix production in rat mesangial cells in response to platelet-derived growth factor (PDGF) or transforming growth factor-beta (TGF-beta). Stimulation of the cells with PDGF increased the amounts of fibronectin, one of extracellular matrix components. Pretreatment with cepharanthine (0.1-2 microM) suppressed the PDGF-stimulated increase in fibronectin in a dose-dependent manner. At a concentration of 2 microM, the alkaloid almost completely suppressed the production. Under the conditions, the alkaloid inhibited tyrosine phosphorylation of several proteins including PDGF beta receptor in PDGF-stimulated cells, and also tyrosine kinase activity of the receptor prestimulated with PDGF in a cell-free assay system. Furthermore, cepharanthine suppressed TGF-beta-stimulated fibronectin production at the same concentration ranges. Our results suggest that cepharanthine inhibits fibronectin production induced by growth factors, probably through suppression of receptor autophosphorylation.
Hayama
M
M
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan.
Inoue
R
R
Akiba
S
S
Sato
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002474:Cell-Free System; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015151:Immunoblotting; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D052117:Benzodioxoles
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D014443:Tyrosine; C006947:cepharanthine; D052117:Benzodioxoles; C099852:PDGF receptor tyrosine kinase