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J Biol Chem, Vol. 274, Issue 30, 20874-20878, July 23, 1999
Type II
Receptor-mediated Manner
,
,
,
, and
From the Mesangial cells share features with contractile
smooth muscle cells and mechanically support the capillary wall. The
role of vitamin D compounds and the transforming growth factor-
Division of Molecular Medicine for Adult and
Geriatric Diseases,
(TGF-
) type II receptor in modulating the smooth muscle phenotype of cultured mesangial cells was examined. Cell proliferation was significantly inhibited by the vitamin D analog
22-oxa-1,25-dihydroxyvitamin D3 (22-oxacalcitriol;
OCT) rather than by 1,25-dihydroxyvitamin D3
(1,25(OH)2D3) in a dose-dependent
manner. OCT-treated early passage mesangial cells (MC-E cells) had
increased expression levels of type IV collagen and smooth muscle
actin mRNA, but 1,25(OH)2D3-treated MC-E
cells did not. The addition of a TGF-
1-neutralizing antibody to the OCT-treated MC-E cells blocked this inhibitory effect
for cell proliferation and attenuated the up-regulated mRNA levels.
However, after exposure to 1,25(OH)2D3 or OCT,
there was no significant difference in the secretion of active TGF-
. We next investigated whether TGF-
type II receptor (RII) was involved in this regulation. OCT treatment significantly increased the
expression of the RII mRNA in MC-E cells. These results suggest that the vitamin D analog OCT induces smooth muscle phenotypic alterations and that this phenomenon was mediated through the induction
of RII in cultured mesangial cells.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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