鼻病毒（RV）是引起哮喘加重的首要病原体，但致病机制未明。我们研究发现，CD151在哮喘病人中表达上调，可能参与气道重塑。RV感染能否引起气道中CD151表达改变？预实验结果显示，RV感染哮喘模型小鼠中，CD151在气道结构细胞中表达显著上调，且与气道重塑的程度呈正相关。那么CD151介导RV诱导哮喘加重的机制是什么？进一步预实验显示，RV感染气道上皮细胞后释放的FGF2可上调CD151，激活和加强integrin αvβ3通路从而活化成纤维细胞，导致气道重塑。由此拟解决的核心科学问题：CD151是否是RV感染所致气道重塑的关键因子。我们拟进一步：明确CD151与RV诱导气道重塑的关联；分析RV感染如何诱导CD151的表达和功能；探讨可能的下游信号转导机制；验证以CD151为哮喘治疗靶点的可行性。项目的开展有望揭示CD151介导RV诱发型哮喘加重的分子机制，为寻找新的治疗靶点提供理论依据。

Viral respiratory infections are associated with the virus-induced asthma in adults as well as children. Human rhinovirus (RV) is a major pathogen of the virus-induced asthma exacerbation. However, the holistic understanding of how RV infection contributes to the asthma exacerbation is incomplete. We have reported that, CD151, a member of the tetraspanin superfamily, is upregulated in the airway structural cells in asthmatic patients’ lung samples and involved in the airway wall remodeling (AWR), a core histological feature of asthma. Based on these observations, we wonder whether the upregulation of CD151 in airway cells can be induced by RV infection. Our preliminary data showed that, CD151 was upregulated in the lungs of RV-ovalbumin (OVA) asthmatic mice. Furthermore, its expression was positively correlated with the degree of AWR, which warrants the further exploration of the underlying mechanism of CD151 modulating AWR process in RV-induced asthma exacerbation. To this end, our preliminary data showed that, upon RV infection, the overexpression of fibroblast growth factor 2 (FGF2) produced by airway epithelial cells was detected, and led to the elevated expression of CD151, and then amplified the FGF2 signaling through complexing with integrin αvβ3 in fibroblasts, the predominant profibrotic airway structural cell, and lead to its hyperplasia, extra cellular matrix (ECM) secretion and differentiation into myofibroblasts, and thus contribute to the AWR. On top of that, we hypothesize that RV-induced AWR effects upon is mediated by the key molecule CD151, through activation and positive feedback of FGF2-CD151-integrin αvβ3 signaling pathway in fibroblast. In this proposed study, we aim to 1) clarify the correlation between RV infection and CD151 expression during AWR; 2) investigate how the RV infection induce the overexpression of CD151 and its pathophysiological role during AWR; 3) explore the CD151 downstream signaling pathway(s); and 4) test the potential of CD151 as a pharmaceutical target in asthma prevention and control. This study holds the promise for elucidating the mechanism of CD151-mediated RV-induced asthma exacerbation, and exploration of CD151 as a novel pharmaceutical target.