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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- Type II Receptor-mediated Manner

Hideharu Abe, Noriyuki Iehara, Kazumasa Utsunomiya, Toru Kita, and Toshio Doi^§

From the  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- (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.

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