T-kininogen can either induce or inhibit proliferation in Balb/c 3T3 fibroblasts, depending on the route of administration.
T-kininogen (T-KG) is a precursor of T-kinin, the most abundant kinin in rat serum, and also acts as a strong and specific cysteine proteinase inhibitor. Its expression is strongly induced during aging in rats, and expression of T-KG in Balb/c 3T3 fibroblasts results in inhibition of cell proliferation. However, T-KG is a serum protein produced primarily in the liver, and thus, most cells are only exposed to the protein from the outside. To test the effect of T-KG on fibroblasts exposed to exogenous T-KG, we purified the protein from the serum of K-kininogen-deficient Katholiek rats. In contrast to the results obtained by transfection, exposure of Balb/c 3T3 fibroblasts to exogenously added T-KG leads to a dose-dependent increase in [3H]-thymidine incorporation. This response does not require kinin receptors, but it is clearly mediated by activation of the ERK pathway. As a control, we repeated the transfection experiments, using a different promoter. The results are consistent with our published data showing that, under these circumstances, T-KG inhibits cell proliferation. We conclude that T-KG exerts opposite effects on fibroblast proliferation, depending exclusively on the way that it is administered to the cells (transfection versus exogenous addition).
Aravena
M
M
Programa de Biología Celular y Molecular, Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Independencia 1027, Santiago, Chile.
Pérez
C
C
Pérez
V
V
Acuña-Castillo
C
C
Gómez
C
C
Leiva-Salcedo
E
E
Nishimura
S
S
Sabaj
V
V
Walter
R
R
Sierra
F
F
D000375:Aging / Q000378:metabolism; D000818:Animals; D041702:BALB 3T3 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007704:Kininogens / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D051381:Rats; D014162:Transfection
D015853:Cysteine Proteinase Inhibitors; D007704:Kininogens; D048049:Extracellular Signal-Regulated MAP Kinases