JBC Invitrogen Ultrasensitive Cytokine Assays

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J Biol Chem, Vol. 274, Issue 30, 20874-20878, July 23, 1999

A Vitamin D Analog Regulates Mesangial Cell Smooth Muscle Phenotypes in a Transforming Growth Factor-beta Type II Receptor-mediated Manner

Hideharu AbeDagger , Noriyuki IeharaDagger , Kazumasa UtsunomiyaDagger , Toru KitaDagger , and Toshio Doi§

From the Dagger  Division of Molecular Medicine for Adult and Geriatric Diseases, Department of Clinical Bio-Regulatory Science and the § Division of Artificial Kidneys, Faculty of Medicine, Kyoto University, Kyoto 606-8397, Japan

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 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 alpha  actin mRNA, but 1,25(OH)2D3-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)2D3 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.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.



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