MicroRNA-216b actively modulates diabetic angiopathy through inverse regulation on FZD5

作者：Dai, Yuxiang; Lu, Hao; Wang, Shen; Chang, Shufu; Li, Chenguang; Huang, Zheyong; Zhang, Feng; Yang, Hongbo; Shen, Yi; Chen, Zhangwei; Qian, Juying; Ge, Junbo^*

来源：Gene, 2018, 658: 129-135.

DOI：10.1016/j.gene.2018.02.050

• Type-II diabetes
• Microvascular, endothelial
• miR-216b
• FZD5
• Angiopathy

Background: In this work, we examined the angiogenic function of microRNA-216b in an in vitro rat diabetic model of myocardial microvascular endothelial cells (MMECs). @@@ Methods: MMECs were extracted from Wistar rats (MMEC(WI)) or diabetic Goto-Kakizaki (GK) rats (MMEC(GK)) and cultured in vitro. QRT-PCR was applied to compare miR-216b between MMEC(WI) and MMEC(GK). MiR-216b was downregulated in MMEC(GK). Its effects on angiogenic development, including invasion and proliferation, were evaluated. In MMEC(GK), putative miR-216b downstream target gene, frizzled class receptor 5 (FZD5), was evaluated by dual-luciferase reporter, qRT-PCR and western blot assays, respectively. FZD5 was further downregulated in MMEC(GK) with stable miR-216b downregulation to evaluate its functional role in regulating diabetic angiogenesis. @@@ Results: MiR-216b was markedly overexpressed in MMEC(GK). MiR-216b downregulation significantly enhanced angiogenesis in MMEC(GK) by promoting invasion and proliferation. FZD5 was inversely upregulated in miR-216b-downregulated MMEC(GK). Subsequently, FZD5 downregulation suppressed angiogenic development, by inhibiting invasion and proliferation in miR-216b-downregulated MMEC(GK). @@@ Conclusion: MicroRNA-216b was overexposed in diabetic MMECs and its downregulation may actively enhance angiogenesis in diabetic angiopathy through inverse regulation on FZD5.

• 出版日期2018-6-5
• 单位复旦大学; 浙江中医药大学