H. Abe et al., A vitamin D analog regulates mesangial cell smooth muscle phenotypes in a transforming growth factor-beta type II receptor-mediated manner, J BIOL CHEM, 274(30), 1999, pp. 20874-20878
Mesangial cells share features with contractile smooth muscle cells and mec
hanically support the capillary wall. The role of vitamin D compounds and t
he transforming growth factor-beta (TGF-beta) type II receptor in modulatin
g the smooth muscle phenotype of cultured mesangial cells was examined. Cel
l proliferation was significantly inhibited by the vitamin D analog 22-oxa-
1,25-dihydroxyvitamin D-3 (22-oxacalcitriol; OCT) rather than by 1,25-dihyd
roxyvitamin D-3 (1,25(OH)(2)D-3) in a dose-dependent manner. OCT-treated ea
rly passage mesangial cells (MC-E cells) had increased expression levels of
type IV collagen and smooth muscle alpha actin mRNA, but 1,25(OH)(2)D-3-tr
eated MC-E cells did not. The addition of a TGF-beta(1)-neutralizing antibo
dy to the OCT-treated MC-E cells blocked this inhibitory effect for cell pr
oliferation and attenuated the up-regulated mRNA levels. However, after exp
osure to 1,25(OH),D, or OCT, there was no significant difference in the sec
retion of active TGF-beta. We next investigated whether TGF-beta type II re
ceptor (RII) was involved in this regulation. OCT treatment significantly i
ncreased the expression of the RII mRNA in MC-E cells. These results sugges
t that the vitamin D analog OCT induces smooth muscle phenotypic alteration
s and that this phenomenon was mediated through the induction of RII in cul
tured mesangial cells.