Vitamin D - a new treatment for airway remodelling in asthma?
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.
Clifford
Rachel L
RL
Centre for Respiratory Research, University of Nottingham, UK.
Knox
Alan J
AJ
D056151:Airway Remodeling / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D016503:Drug Delivery Systems; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D014808:Vitamin D Deficiency; D014815:Vitamins / Q000494:pharmacology*
D005938:Glucocorticoids; D018167:Receptors, Calcitriol; D014815:Vitamins; D003907:Dexamethasone; D002117:Calcitriol