期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2019, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2019/6326517
关键词
-
类别
资金
- National Natural Science Foundation of China [81573993, 81774334]
Fibroblast-like synoviocytes (FLSs) are the main effector cells of knee osteoarthritis (KOA) synovial fibrosis. Our last report showed that NLRP1 and NLRP3 inflammasomes may mediate LPS/ATP-induced FLSs pyroptosis in KOA. In the present study, we found an elevated hypoxia-inducible factor-1 alpha (HIF-1 alpha) level in the synovial tissue of KOA model rats, and inhibiting the increase of HIF-1 alpha could improve synovial fibrosis in rats. Subsequently, we established LPS/ATP-induced model in FLSs mimicking the inflammatory environment of KOA. FLSs transfected with siRNA HIF-1 alpha showed a reduced cell death; meanwhile, the relative expression of pyroptosis-related proteins was also downregulated. Additionally, FLSs transfected with or without siRNA GSDMD were exposed to hypoxia. GSDMD silencing can significantly reduce both gene and protein levels of fibrogenic markers transforming growth factor-beta (TGF-beta), procollagen-lysine, 2-oxoglutarate 5-dioxygenase2 (PLOD2), collagen type I alpha 1 chain (COL1A1), and tissue inhibitor of metalloproteinases 1 (TIMP1). Taken together, our findings indicate that increased HIF-1 alpha is highly involved in the KOA synovial fibrosis. Moreover, elevated HIF-1 alpha may aggravate synovial fibrosis via FLS pyroptosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据