[Retracted] MicroRNA‐133b Inhibition Restores EGFR Expression and Accelerates Diabetes‐Impaired Wound Healing

Abstract

Diabetic foot ulcers (DFUs) are caused by impairments in peripheral blood vessel angiogenesis and represent a great clinical challenge. Although various innovative techniques and drugs have been developed for treating DFUs, therapeutic outcomes remain unsatisfactory. Using the GEO database, we obtained transcriptomic microarray data for DFUs and control wounds and detected a significant downregulation of epidermal growth factor receptor (EGFR) in DFUs. We cultured human umbilical vein endothelial cells (HUVECs) and noted downregulated EGFR expression following high-glucose exposure in vitro. Further, we observed decreased HUVEC proliferation and migration and increased apoptosis after shRNA-mediated EGFR silencing in these cells. In mice, EGFR inhibition via focal EGFR-shRNA injection delayed wound healing. Target prediction analysis followed by dual-luciferase reporter assays indicated that microRNA-133b (miR-133b) is a putative upstream regulator of EGFR expression. Increased miR-133b expression was observed in both glucose-treated HUVECs and wounds from diabetes patients, but no such change was observed in controls. miR-133b suppression enhanced the proliferation and angiogenic potential of cultured HUVECs and also accelerated wound healing. Although angiogenesis is not the sole mechanism affected in DFU, these findings suggest that the miR-133b-induced downregulation of EGFR may contribute to delayed wound healing in diabetes. Hence, miR-133b inhibition may be a useful strategy for treating diabetic wounds.

The progress and challenges of circRNA for diabetic foot ulcers: A mini-review

“…In addition, they found that hsa_circ_0084443 in HEKs can mediate the biological effects of PI3K, EGFR and ERK signaling pathways, but blocking these signaling pathways can inhibit the migration of HEKs (43). PI3K, EGFR and ERK signaling pathways are relatively mature and well-recognized effective pathways in the DFU healing process (69)(70)(71), which also laterally proves that circ_0084443 may play a key role in ulcer healing. SRTING database is a powerful online website for analyzing protein interactions (PPI network).…”

Bioinformatics analysis of ferroptosis-related genes in the pathogenesis of diabetic ulcers

“…These ve hub genes have a good performance in the prediction and diagnosis of diabetic ulcers. A previous study found that EGRF knockdown decreased the proliferative capacity of cells and delayed the healing of fullthickness of back wounds in vivo 23 . Solute carrier family 2 member 1 (SLC2A1) has been related to diabetic microvascular complications in multiple projects 24 ; 25 .…”

Innovative Treatment Strategies to Accelerate Wound Healing: Trajectory and Recent Advancements

“…Furthermore, miR-497 accelerated diabetic wound healing by decreasing the pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and enhanced wound closure [ 329 ]. In another study, the inhibition of miR-133b resulted in accelerated wound healing in diabetes-impaired wound healing through the restoration of epidermal growth factor receptor (EGFR) expression and angiogenesis [ 330 ]. In a recent study, exosomal-cargoed miRs demonstrated a pivotal role in modulating angiogenesis in diabetic wound healing by regulating the expression of VEGF and downstream signaling transduction [ 303 ].…”