Asthma is a chronic and heterogeneous disease characterised by airway inflammation and intermittent airway narrowing. The key obstacle in the prevention and treatment of asthma has been our incomplete understanding of its aetiology and biological mechanisms. The ras homolog family member A (RhoA) of the Rho family GTPases has been considered to be one of the most promising and novel therapeutic targets for asthma. It is well known that RhoA/Rho-kinases play an important role in the pathophysiology of asthma, including airway smooth muscle contraction, airway hyper-responsiveness, β-adrenergic desensitisation and airway remodelling. However, recent advances have suggested novel roles for RhoA in regulating allergic airway inflammation. Specifically, RhoA has been shown to regulate allergic airway inflammation through controlling Th2 or Th17 cell differentiation and to regulate airway remodelling through regulating mesenchymal stem cell (MSC) differentiation. In this review, we evaluate the literature regarding the recent advances in the activation of RhoA/Rho-kinase, cytokine and epigenetic regulation of RhoA/Rho-kinase, and the role of RhoA/Rho-kinase in regulating major features of asthma, such as airway hyper-responsiveness, remodelling and inflammation. We also discuss the importance of the newly identified role of RhoA/Rho-kinase signalling in MSC differentiation and bronchial epithelial barrier dysfunction. These findings indicate the functional significance of the RhoA/Rho-kinase pathway in the pathophysiology of asthma and suggest that RhoA/Rho-kinase signalling may be a promising therapeutic target for the treatment of asthma.

中文翻译：

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哮喘中的RhoA / Rho激酶：从发病机理到治疗靶点。

哮喘是一种慢性异质性疾病，其特征在于气道炎症和间歇性气道狭窄。预防和治疗哮喘的主要障碍是我们对其病因和生物学机制的不完全了解。Rho家族GTPases的ras同源家族成员A（RhoA）被认为是哮喘最有希望和新颖的治疗靶标之一。众所周知，RhoA / Rho激酶在哮喘的病理生理中起着重要作用，包括气道平滑肌收缩，气道高反应性，β-肾上腺素脱敏和气道重塑。但是，最近的进展表明RhoA在调节过敏性气道炎症中的新作用。特别，RhoA已显示可通过控制Th2或Th17细胞分化来调节过敏性气道炎症，并通过调节间充质干细胞（MSC）分化来调节气道重塑。在这篇综述中，我们评估了有关RhoA / Rho激酶激活，RhoA / Rho激酶的细胞因子和表观遗传调控的最新进展以及RhoA / Rho激酶在调节哮喘主要特征中的作用的文献，例如如气道反应过度，重塑和发炎。我们还讨论了新发现的RhoA / Rho激酶信号在MSC分化和支气管上皮屏障功能障碍中的作用的重要性。