摘要 : Over-expression ofWISP1 has been described in multi-organ fibrosis and tissue remodeling. Moreover, it has recently been found that polymorphismofWISP1 gene is relatedwith the change of lung function in asthmatic subjects. Therefo... 展开 Over-expression ofWISP1 has been described in multi-organ fibrosis and tissue remodeling. Moreover, it has recently been found that polymorphismofWISP1 gene is relatedwith the change of lung function in asthmatic subjects. Therefore,we hypothesized thatWISP1might be closely linked to occurrence and development of asthmatic airway remodeling. Aim of this study was to examine the roles ofWISP1 in an asthmatic model with airway remodeling and assess the specific effects ofWISP1 on human lung fibroblast in vitro. Animal models were developed by challengedwith ovalbumin. The levels ofWISP1 expression in animal modelswere assessed by real-time PCR and immunohistochemistry. To examine the specific effects of WISP1 on airway remodeling, WISP1 was depleted by neutralizingaα-WISP1 antibodies in vivo.Moreover, human lung fibroblast (HFL-1)was challengedwith WISP1 in the presence and absence of SH-5 in vitro. Our study showed that OVA exposure increased the levels of WISP1 expression in a rat asthma model.WISP1 depletion could partially inhibit OVA-induced airway remodeling. In vitro, WISP1-treated HFL-1 cells presented abnormal proliferation and over-expression of Col1a1 and Fn1. However, WISP1-induced collagen release from HFL-1 cells could be attenuated by pretreatment with an Akt inhibitor. Moreover, the levels of p-Akt and p-GSK-3β in WISP1-treated HFL-1 cells were also significantly elevated. In summary, WISP1 might initiate and perpetuate the pathological remodeling of asthma by inducing fibroblast proliferation and ECM deposition. The specific effects of WISP1 were likely due to activation of pulmonary Akt/GSK-3β signaling. 收起