A vitamin D analog regulates mesangial cell smooth muscle phenotypes in a transforming growth factor-beta type II receptor-mediated manner.
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-beta (TGF-beta) 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 D(3) (22-oxacalcitriol; OCT) rather than by 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) 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 alpha actin mRNA, but 1, 25(OH)(2)D(3)-treated MC-E cells did not. The addition of a TGF-beta(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)(2)D(3) or OCT, there was no significant difference in the secretion of active TGF-beta. We next investigated whether TGF-beta 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.
Division of Molecular Medicine for Adult and Geriatric Diseases, Department of Clinical Bio-Regulatory Science, Faculty of Medicine, Kyoto University, Kyoto 606-8397, Japan.
H
H
Abe
N
N
Iehara
K
K
Utsunomiya
T
T
Kita
T
T
Doi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D002120:Calcium Channel Agonists; D018125:Receptors, Transforming Growth Factor beta; D002117:Calcitriol; C051883:maxacalcitol