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MicroRNA-221-3p Targets THBS1 to Promote Wound Healing in Diabetes.


ABSTRACT:

Introduction

Diabetes foot ulcer (DFU) is a serious complication of diabetes characterized with chronic foot ulceration, poor wound healing (WH), and persistent inflammation. MiR-221-3p, as microRNA, has been shown to accelerate WH in previous study, but the underlying mechanisms are poorly understood.

Methods

In this study, we aimed to determine how miR-221-3p influences WH by targeting THBS1. The effect of miRNA-221-3p on wound healing of diabetes by epidermal injection of miRNA-221-3p agomir. In vitro generated human immortalized keratinocytes (HaCaT cells) were transfected with miR-mimics and negative control with high glucose treatment. The effects of miRNA-221-3p on cell apoptosis and angiogenesis using cell apoptosis assay and the tube formation assay, respectively. Direct target interaction of miR-221-3p and predicted target sites in 3'UTR of THBS1 were examined by luciferase reporter gene assay. Breeding miRNA-221 knockout mice for experimental verification.

Results

We found that miRNA-221-3p overexpression at the wound edge of normal mice and diabetes mice can promote WH. As contrast, WH of miR-221 knockout mice delayed with increased epithelial apoptosis and reduced angiogenesis in the dermis. miR-221-3p was found to inhibit apoptosis in HaCaT cells, and enhanced angiogenesis in human umbilical vein endothelial cells (HUVECs) that were co-cultured. Bioinformatics analysis as well as the dual-luciferase reporter assay revealed miR-221-3p to target 3' untranslated region of THBS1.

Conclusion

Our findings suggested miR-221-3p might exert an essential impact on diabetes WH via inhibition of THBS1 and lack of miR-221-3p possibly results in impaired healing in chronic wounds of type 2 diabetes. Therefore, developing medicine such as chemically modified analogs of miR-221-3p in future could benefit patients with DFU.

SUBMITTER: Hu K 

PROVIDER: S-EPMC10503564 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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MicroRNA-221-3p Targets THBS1 to Promote Wound Healing in Diabetes.

Hu Keyan K   Liu Xueying X   Chang Hongfeng H   Zhang Yi Y   Zhou Hui H   Liu Lei L   Zhang Xin X   Jiao Ziying Z   Shen Bing B   Zhang Qiu Q  

Diabetes, metabolic syndrome and obesity : targets and therapy 20230911


<h4>Introduction</h4>Diabetes foot ulcer (DFU) is a serious complication of diabetes characterized with chronic foot ulceration, poor wound healing (WH), and persistent inflammation. MiR-221-3p, as microRNA, has been shown to accelerate WH in previous study, but the underlying mechanisms are poorly understood.<h4>Methods</h4>In this study, we aimed to determine how miR-221-3p influences WH by targeting THBS1. The effect of miRNA-221-3p on wound healing of diabetes by epidermal injection of miRNA  ...[more]

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