TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling

Abstract

Background Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated. Methods We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses. Results We found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis. Conclusions Our findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.

Hsa_circ_0001020 accelerates the lower extremity deep vein thrombosis via sponging miR-29c-3p to promote MDM2 expression

“…Based on the online J o u r n a l P r e -p r o o f databases, ENCORI for RNA interactomes (http://starbase.sysu.edu.cn/), predicated the potential candidates for hsa_circ_0001020. MiR-29c-3p is one of the predicated candidates for hsa_circ_0001020, and exerts an important role in regulating EPC function [21], therefore, we focused on the expression and function of miR-29c-3p in subsequent experiments. We found miR-29c-3p significantly reduced in peripheral blood from DVT patients compared with health control (Figure 3A).…”

Emerging Roles of Long Non-Coding RNAs in Diabetic Foot Ulcers

“…63 In the study by Li et al, overexpression of lncRNA taurine upregulated gene 1 (TUG1) restored the ability of migration, invasion, and tube formation in high-glucose treated EPCs. 64 In vivo, TUG1 overexpression promoted angiogenesis in a diabetic mouse ischemic limb model.…”

Long noncoding RNA TUG1 upregulates VEGFA to enhance malignant behaviors in stomach adenocarcinoma by sponging miR‐29c‐3p

“…Many studies reported that TUG1 is involved in angiogenesis during the progression of various diseases 18,19 . One miRNA in particular, miR‐29c‐3p, could be directly targeted by TUG1 to stimulate angiogenesis in endothelial progenitor cells and diabetic mouse ischemic limb 20 . Besides, previous studies showed that TUG1 exerts oncogenic functions by interacting with miR‐29c‐3p in several cancers 9,21 .…”

“… 18 , 19 One miRNA in particular, miR‐29c‐3p, could be directly targeted by TUG1 to stimulate angiogenesis in endothelial progenitor cells and diabetic mouse ischemic limb. 20 Besides, previous studies showed that TUG1 exerts oncogenic functions by interacting with miR‐29c‐3p in several cancers. 9 , 21 Additionally, it has been reported that miR‐29c‐3p could suppress cell proliferation and induce apoptosis in lung cancer by targeting angiogenic factor VEGFA.…”