目的通过RNA干扰技术阻断人骨关节炎呈现OA滑膜细胞WISP-1信号通路,探索其在骨关节炎治疗中的应用前景。方法根据干扰RNA设计原则,合成并构建WISP-1 sh RNA质粒表达载体。将质粒表达载体转染入滑膜细胞并分组。转染24 h后测定细胞β-cat...目的通过RNA干扰技术阻断人骨关节炎呈现OA滑膜细胞WISP-1信号通路,探索其在骨关节炎治疗中的应用前景。方法根据干扰RNA设计原则,合成并构建WISP-1 sh RNA质粒表达载体。将质粒表达载体转染入滑膜细胞并分组。转染24 h后测定细胞β-catenin、WISP-1、MMP-3 m RNA相对表达水平。结果 OA滑膜细胞经过RNAi后WISP-1、MMP-3表达明显减少,意味着干扰WISP-1使得Wnt/β-catenin通路对MMP-3的诱导作用降低,也进一步证实了Wnt/β-atenin/WISP-1通路的存在。因此,WISP-1可以作为治疗骨关节炎一个理想的靶点。结论本实验中我们观察到,OA滑膜细胞经过RNAi后MMP-3表达明显减少,意味着Wnt/β-连环蛋白信号通路对MMP-3的诱导作用降低,进一步证实了Wnt/β-连环蛋白(catenin)/WISP-1通路的存在。展开更多
Wnt-1 inducible signaling pathway-1(WISP-1), also known as CCN-4, belongs to the connective tissue growth factor(CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ d...Wnt-1 inducible signaling pathway-1(WISP-1), also known as CCN-4, belongs to the connective tissue growth factor(CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer,cholangiocarcinoma, hepatocellular carcinoma and breast cancer. However, interestingly, WISP-1 exerts a tumorsuppressing role in lung and prostate cancers. WISP-1 promotes cell proliferation, adhesion, motility, invasion,metastasis and epithelial-to-mesenchymal transition via particular signaling pathways. In this review, we discussed the structure, expression profile, functions, clinical significance and potential mechanisms of WISP-1 in cancer and non-neoplastic diseases.展开更多
文摘目的通过RNA干扰技术阻断人骨关节炎呈现OA滑膜细胞WISP-1信号通路,探索其在骨关节炎治疗中的应用前景。方法根据干扰RNA设计原则,合成并构建WISP-1 sh RNA质粒表达载体。将质粒表达载体转染入滑膜细胞并分组。转染24 h后测定细胞β-catenin、WISP-1、MMP-3 m RNA相对表达水平。结果 OA滑膜细胞经过RNAi后WISP-1、MMP-3表达明显减少,意味着干扰WISP-1使得Wnt/β-catenin通路对MMP-3的诱导作用降低,也进一步证实了Wnt/β-atenin/WISP-1通路的存在。因此,WISP-1可以作为治疗骨关节炎一个理想的靶点。结论本实验中我们观察到,OA滑膜细胞经过RNAi后MMP-3表达明显减少,意味着Wnt/β-连环蛋白信号通路对MMP-3的诱导作用降低,进一步证实了Wnt/β-连环蛋白(catenin)/WISP-1通路的存在。
基金supported by the Young Talents of Science and Technology Support Project of Colleges and Universities of Inner Mongolia Autonomous Region (NJYT-12-B21, 2012)the Great Project of the Affiliated Hospital of Inner Mongolia Medical University, China, 2012 (No. NYFY ZD 2012014)Beijing Municipal Administration of Hospitals’ Youth Programme (QML20151003)
文摘Wnt-1 inducible signaling pathway-1(WISP-1), also known as CCN-4, belongs to the connective tissue growth factor(CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer,cholangiocarcinoma, hepatocellular carcinoma and breast cancer. However, interestingly, WISP-1 exerts a tumorsuppressing role in lung and prostate cancers. WISP-1 promotes cell proliferation, adhesion, motility, invasion,metastasis and epithelial-to-mesenchymal transition via particular signaling pathways. In this review, we discussed the structure, expression profile, functions, clinical significance and potential mechanisms of WISP-1 in cancer and non-neoplastic diseases.