Nephrology Dialysis Transplantation, Vol 12, Issue 4 694-700, Copyright © 1997 by Oxford University Press
S Higueruelo and R Romero
BACKGROUND: Mesangial cell proliferation is an important feature of chronic
glomerular disease. Different cytokines and vasoactive substances have been
implicated in mesangial cell proliferation. However, the role of
angiotensin II remains controversial. Furthermore, all the studies made to
date have been performed using a medium supplemented with high
concentrations of insulin (5 micrograms/ml) in order to facilitate
mesangial cell proliferation in vitro. As has recently been reported,
insulin causes a change both in extracellular matrix composition and in
mesangial cell phenotype, thus mimicking disease conditions. METHODS: We
examined the effects of Ang II in synchronized and proliferating mesangial
cells with and without growth factor (PDGF-BB, bFGF and/or insulin)
supplementation and the effects of exogenous administration of insulin on
mesangial proliferation by measuring the bromodeoxyuridine (BrdU) uptake.
RESULTS: Angiotensin II itself caused no increase in BrdU incorporation.
However, it exerted a significant synergistic effect on PDGF-BB-induced DNA
synthesis (P < 0.05) in quiescent medium and tended to stimulate BrdU
uptake by proliferating cells (P = 0.09). BrdU incorporation significantly
correlated with direct cell count (r = 0.95). PDGF-BB had the maximal
stimulatory effect on DNA synthesis both in quiescent and in proliferative
culture conditions. The insulin dose (5 micrograms/ml) which has been shown
to cause mesangial cell proliferation in vitro, caused an increase in BrdU
incorporation by itself in quiescent medium. CONCLUSIONS: We conclude that
in an insulin-free medium, mimicking in vivo glomerular conditions, PDGF-BB
or proliferative medium are needed to allow Ang II-induced DNA synthesis in
mesangial cell culture.
ORIGINAL ARTICLES
Angiotensin II requires PDGF-BB to induce DNA synthesis in rat mesangial cells cultured in an exogenous insulin-free medium
Nephrology Unit, Hospital Universitario Germans Trias i Pujol, Badalona, Spain.
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