Centre for Respiratory Research, University of Nottingham, UK.
Br J Pharmacol. 2009 Nov;158(6):1426-8. doi: 10.1111/j.1476-5381.2009.00429.x.
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.
气道平滑肌（ASM）质量的增加在慢性哮喘气道重塑中起着关键作用。ASM 细胞肥大和增生可能导致 ASM 质量增加，并且多种有丝分裂原在细胞培养中诱导 ASM 增殖。最近人们认识到维生素 D 广泛缺乏，并在许多细胞上鉴定出维生素 D 受体，这表明维生素 D 可能是包括癌症、感染和哮喘在内的许多疾病的潜在治疗靶点。在本期《英国药理学杂志》上，Damera 等人表明，1,25-二羟维生素 D3（calcitriol），一种维生素 D 受体的甾体调节剂，可抑制凝血酶和血小板衍生生长因子诱导的 ASM 细胞增殖。他们还出人意料地表明，糖皮质激素地塞米松可增强有丝分裂原诱导的 ASM 增殖。他们的研究结果开始阐明 calcitriol 抑制细胞增殖所利用的分子机制，并表明视网膜母细胞瘤蛋白的过度磷酸化和检查点激酶 1（Chk1）的激活对这一过程至关重要。这项研究确定了维生素 D 抑制 ASM 增殖的作用是一种细胞效应，并支持了维生素 D 是治疗哮喘气道重塑的潜在方法的假说。
