Abstract

Increased airway smooth muscle (ASM) mass plays a critical role in chronic asthmatic airway remodelling. ASM cell hypertrophy and hyperplasia are likely to contribute to increased ASM mass and a variety of mitogens induce ASM proliferation in cell culture. Recent recognition of widespread vitamin D deficiency and identification of the vitamin D receptor on many cells has implicated vitamin D as a potential therapeutic target for many disorders including cancer, infection and asthma. In this issue of British Journal of Pharmacology, Damera et al. show that calcitriol, a secosteroidal modulator of vitamin D receptors, inhibited thrombin and platelet-derived growth factor-induced ASM cell proliferation. They also, perhaps surprisingly, show the glucocorticoid dexamethasone to potentiate mitogen-induced ASM proliferation. Their results begin to elucidate the molecular mechanism(s) utilized by calcitriol to inhibit cell proliferation and suggest hyperphosphorylation of retinoblastoma protein and activation of checkpoint kinase 1 (Chk1) as critical to this process. This study identifies inhibition of ASM proliferation as a cellular effect of vitamin D and supports the hypothesis that vitamin D is a potential treatment for airway remodelling in asthma.

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