PDGF-BB, but not PDGF-AA, stimulates calcium mobilization, activation of calcium channels and cell proliferation in cultured rat mesangial cells.
The effects of different isoforms of platelet-derived growth factor (PDGF) on cellular growth and on cytoplasmic Ca2+ levels in mesangial cells using a microfluorometric system and the calcium indicator FURA-2 were investigated. A rapid increase of cytoplasmic calcium in response to PDGF-BB was found and in the presence of 1.25 mM extracellular calcium, the resting level of cytoplasmic calcium following the initial peak was significantly increased compared with a calcium-free medium, but was completely attenuated with the calcium channel blocker verapamil (50 microM). PDGF-AA did not cause any increase in cytoplasmic calcium. In growth arrested MC PDGF-BB, but not PDGF-AA, also enhanced cell growth. It is concluded that cultured rat mesangial cells react to PDGF-BB but not to PDGF-AA with a rapid mobilization of intracellular calcium followed by subsequent activation of calcium channels and a stimulation of cell growth. A PDGF-BB driven mechanism for MC proliferation in inflammatory and metabolic glomerular diseases is suggested.
Wallmon
A
A
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Fellström
B
B
Larsson
R
R
Floege
J
J
Topley
N
N
Ljunghall
S
S
D000818:Animals; D000077214:Becaplermin; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002455:Cell Division; D003593:Cytoplasm / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins
D015220:Calcium Channels; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D002118:Calcium