AJP - Renal Physiology, Vol 259, Issue 5 768-F777, Copyright © 1990 by American Physiological Society
Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells
G. Wolf and E. G. Neilson
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
In the present study we demonstrate that a murine proximal tubular cell
line (MCT cells), expressing angiotensin II (ANG II) receptors
[dissociation constant (Kd) = 0.89 nM; receptor density (R0) = 46,900
receptors/cell] in culture, can be induced to hypertrophy after the daily
addition of exogenous ANG II (10(-8) M). This hypertrophic response was
characterized by an increase in total cellular protein content, by an
enhancement of [3H]leucine incorporation into precipitable proteins, and by
an augmentation in cell size by cytofluorography. This ANG II effect
producing MCT cell enlargement was demonstrable in the absence of cellular
proliferation. Proliferation of MCT cells, however, could be induced by
epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and
pretreatment of rested MCT cells with ANG II further enhanced EGF-induced
cell division. ANG II-induced hypertrophy in MCT cells was factor specific,
in that it could be blocked with saralasin, and not induced by angiotensin
I (ANG I). This hypertrophic response was also independent of prostaglandin
E2 synthesis but was transducible by pertussis toxin-sensitive G proteins
and involved, to some extent, the activation of Na(+)-H+ exchange. ANG II,
as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes
c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene
activation is probably not a specific prerequisite for hypertrophy. Our
findings demonstrate that ANG II, in culture, can be a single-factor event
capable of inducing hypertrophy in proximal tubular cells.
