Discovery of enzymatically depolymerized heparins capable of treating Bleomycin-induced pulmonary injury and fibrosis in mice

作者：Yan, Yishu; Du, Shanshan; Ji, Yang; Su, Nan; Wang, Yi; Mei, Xiang; Zhu, Wenming; He, Dong; Lu, Yuan; Zhang, Chong; Xing, Xin-Hui^*

来源：Carbohydrate Polymers, 2017, 174: 82-88.

DOI：10.1016/j.carbpol.2017.05.102

• Idiopathic pulmonary fibrosis
• Enzymatic depolymerization
• Heparin
• Heparinases
• Lung injury

Heparin has recently been shown to slow down idiopathic pulmonary fibrosis (IPF) process and improve survival of patients in some cases. To improve the anti-IPF function while minimizing their side effects, we developed heparin libraries with different structures depolymerized by single or combined heparinases, and systematically screened the efficacy of the different heparins for treatment of Bleomycin-induced pulmonary injury and fibrosis using mice model. Then we characterized the structural properties of the components capable of treating pulmonary injury and fibrosis by use of chip-based amide hydrophilic interaction chromatography (HILIC)-fourier transform (FT)-ESIMS, polyacrylamide gel electrophoresis (PAGE), and high performance liquid chromatography (HPLC). Our results showed that the depolymerized heparins with relative higher molecular weight (I-2 and III-2) by the respective heparinase I and III protected mice from the induced pulmonary injury and fibrosis. In addition, the selected depolymerized heparins inhibited high-mobility group protein B1 (HMGB-1) expression, prevented E-cadhesin from downregulation, and reduced fibroblasts accumulation in the mouse lung tissue. Our study suggested that the depolymerized heparins of I-2 and III-2 with the most significant efficacy might target several pathways in alleviating the induced pulmonary fibrosis.

• 出版日期2017-10-15
• 单位清华大学