胸腺基质淋巴细胞生成素（TSLP）在哮喘气道慢性炎症和重塑中有重要作用。新近研究发现，TSLP的亚型长链TSLP（long-TSLP）可促进肺成纤维细胞增殖及合成细胞外基质（ECM），而短链TSLP（short-TSLP）能抑制long-TSLP的作用。然而，long-TSLP和short-TSLP调控肺成纤维细胞增殖及合成ECM的机制尚不清楚。本课题组前期研究工作发现，long-TSLP可促进肺成纤维细胞有氧糖酵解。因此，本课题拟运用CRISPR/Cas9基因敲除、免疫荧光、原位杂交等技术，观察是否long-TSLP通过诱导肺成纤维细胞有氧糖酵解，诱导其增殖及合成ECM，促进气道重塑的发生发展；并进一步探讨long-TSLP通过 TSLPR/IL-7Rα-STAT3/5-HIF-1α上调肺成纤维细胞有氧糖酵解的机制，及short-TSLP在其中的作用。为哮喘气道重塑防治提供新的策略。

Thymic stromal lymphopoietin (TSLP) plays an important role in airway chronic inflammation and remodeling of asthma. Recent reports that the long-TSLP, a subtype of TSLP, could promoted proliferation and extracellular matrix (ECM) production, but the effects of long-TSLP could be inhibited by short-TSLP. However, the mechanism of long-TSLP and short-TSLP in regulating proliferation and ECM of lung fibroblast is unclear. The preliminary study found that aerobic glycolysis was up-regulation by long-TSLP. Therefore, this project would used CRISPR / Cas9 gene knockout, immunofluorescence and in situ hybridization to investigate whether long-TSLP promoted proliferation and ECM through up-regulating aerobic glycolysis of lung fibroblast to participate in the development of airway remodeling. And to further illustrate the specific mechanism of long-TSLP inducing aerobic glycolysis of lung fibroblast by TSLPR/IL-7Rα-STAT3/5-HIF-1α and the effects of short-TSLP in that. These results would provide new theory basis for treatment of asthma.