Growth arrest of a murine mesangial cell line by transforming growth factor beta 1 is associated with inhibition of mitogen-induced Ca2+ mobilization.
Transforming growth factor-beta (TGF beta) is a multifunctional cytokine showing growth effects on many cell types. In the present study effects of TGF beta 1 on mitogen-induced Ca2+ responses were investigated in an immortalized murine mesangial cell line where TGF beta 1 effects on growth are inhibitory. TGF beta 1 was found to inhibit intracellular Ca2+ mobilization induced by platelet-derived growth factor (PDGF). This effect was completely reversed by previous addition of the non-specific serine/threonine kinase inhibitor H-7, but was unaffected by GF 109203X, a specific inhibitor of protein kinase C (PKC). These findings suggest that inhibition of mitogen-induced Ca2+ mobilization by TGF beta 1 appears not to involve prior activation of PKC, but may participate in the mechanisms whereby mesangial cell growth is inhibited by TGF beta 1.
Baffy
G
G
Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia 19104, USA.
Sharma
K
K
Shi
W
W
Ziyadeh
F N
FN
Williamson
J R
JR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005920:Glomerular Mesangium / Q000166:cytology* / Q000201:enzymology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007211:Indoles; D008301:Maleimides; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D002118:Calcium