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小檗碱通过miR-21-3p/RRAGB轴改善内皮祖细胞功能和伤口愈合，用于治疗下肢静脉溃疡。

Berberine ameliorates endothelial progenitor cell function and wound healing and via the miR-21-3p/RRAGB axis for venous leg ulcers.

作者信息

Qiao Wei, Niu Lingying, Jiang Weihua, Lu Li, Liu Jiali

机构信息

Department of Vascular Surgery, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China.

Department of Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China.

出版信息

Regen Ther. 2024 Jul 11;26:458-468. doi: 10.1016/j.reth.2024.06.011. eCollection 2024 Jun.

DOI:10.1016/j.reth.2024.06.011
PMID:39100534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11296065/
Abstract

PURPOSE

Venous leg ulcers (VLUs) are prevalent chronic wounds with limited treatment options. This study aimed to investigate the potential of berberine to enhance endothelial progenitor cell (EPC) function in VLU healing.

METHODS

Histopathological changes and inflammatory cytokine levels in a deep venous thrombosis (DVT) mouse model were assessed using HE staining and ELISA assays. A luciferase reporter assay was employed to identify the miR-21-3p and RRAGB targeting relationship. EPC proliferation, migration, and tube formation were evaluated through CCK-8, Transwell, and tubule formation assays, while the mTOR pathway and autophagy-related proteins were analyzed by immunofluorescence staining and western blotting.

RESULTS

Berberine significantly improved EPC functions, such as proliferation, migration, and tube formation , and enhanced EPC-mediated wound healing in a DVT mouse model. Furthermore, miR-21-3p was downregulated in EPCs from VLU patients, and its overexpression improved model EPC functions. Mechanistically, RRAGB, which regulates the mTOR pathway, was identified as a potential miR-21-3p target in EPCs. Overexpression of RRAGB inhibited autophagic activity and impaired EPC function.

CONCLUSION

Berberine shows promise in ameliorating EPC function and promoting wound healing in VLUs. The regulation of the miR-21-3p/RRAGB axis by berberine could offer a promising therapeutic approach for managing VLUs.

摘要

目的

下肢静脉溃疡（VLU）是常见的慢性伤口，治疗选择有限。本研究旨在探讨小檗碱在VLU愈合中增强内皮祖细胞（EPC）功能的潜力。

方法

采用HE染色和ELISA检测评估深静脉血栓形成（DVT）小鼠模型的组织病理学变化和炎性细胞因子水平。采用荧光素酶报告基因检测法鉴定miR-21-3p与RRAGB的靶向关系。通过CCK-8、Transwell和小管形成实验评估EPC的增殖、迁移和小管形成能力，同时通过免疫荧光染色和蛋白质印迹分析mTOR通路和自噬相关蛋白。

结果

小檗碱显著改善了EPC的功能，如增殖、迁移和小管形成，并增强了DVT小鼠模型中EPC介导的伤口愈合。此外，VLU患者的EPC中miR-21-3p表达下调，其过表达改善了模型EPC的功能。机制上，调控mTOR通路的RRAGB被确定为EPC中潜在的miR-21-3p靶点。RRAGB的过表达抑制了自噬活性并损害了EPC功能。

结论

小檗碱在改善VLU中EPC功能和促进伤口愈合方面显示出前景。小檗碱对miR-21-3p/RRAGB轴的调控可能为VLU的治疗提供一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/fc04fb492fc9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/af5e37a6c586/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/762ed3fa297d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/71826a0594c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/559a88e80dcb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/242f0a407248/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/fc04fb492fc9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/af5e37a6c586/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/762ed3fa297d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/71826a0594c7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/559a88e80dcb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/242f0a407248/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d522/11296065/fc04fb492fc9/gr6.jpg

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