MiR-21 regulating PVT1/PTEN/IL-17 axis towards the treatment of infectious diabetic wound healing by modified GO-derived biomaterial in mouse models

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Abstract

Background

Diabetic foot ulcer (DFU), persistent hyperglycemia and inflammation, together with impaired nutrient and oxygen deficiency, can present abnormal angiogenesis following tissue injury such that these tissues fail to heal properly. It is critical to design a new treatment method for DFU patients with a distinct biomechanism that is more effective than current treatment regimens.

Method

Graphene oxide (GO) was combined with a biocompatible polymer as a kind of modified GO-based hydrogel. The characterization of our biomaterial was measured in vitro. The repair efficiency of the biomaterial was evaluated in the mouse full-skin defect models. The key axis related to diabetic wound (DW) was identified and investigated using bioinformatics analyses and practical experiments.

Result

In the study, we found that our modified GO-based wound dressing material is a promising option for diabetic wound. Secondly, our biomaterial could enhance the secretion of small EVs (sEVs) with more miR-21 by adipose-derived mesenchymal stem cells (AD-MSCs). Thirdly, the PVT1/PTEN/IL-17 axis was found to be decreased to promote DFU wound healing by modifying miR-21 with the discovery of PVT1 as a critical LncRNA by bioinformatics analysis and tests.

Conclusion

These findings could aid in the development of clinical care strategies for DFU wounds.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12951-022-01516-4.

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The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses.

Gil Stelzer, Naomi Rosen, Inbar Plaschkes … (2016)

GeneCards, the human gene compendium, enables researchers to effectively navigate and inter-relate the wide universe of human genes, diseases, variants, proteins, cells, and biological pathways. Our recently launched Version 4 has a revamped infrastructure facilitating faster data updates, better-targeted data queries, and friendlier user experience. It also provides a stronger foundation for the GeneCards suite of companion databases and analysis tools. Improved data unification includes gene-disease links via MalaCards and merged biological pathways via PathCards, as well as drug information and proteome expression. VarElect, another suite member, is a phenotype prioritizer for next-generation sequencing, leveraging the GeneCards and MalaCards knowledgebase. It automatically infers direct and indirect scored associations between hundreds or even thousands of variant-containing genes and disease phenotype terms. VarElect's capabilities, either independently or within TGex, our comprehensive variant analysis pipeline, help prepare for the challenge of clinical projects that involve thousands of exome/genome NGS analyses. © 2016 by John Wiley & Sons, Inc.

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Exosomes Facilitate Therapeutic Targeting of Oncogenic Kras in Pancreatic Cancer

Sushrut Kamerkar, Valerie LeBleu, Hikaru Sugimoto … (2017)

Summary The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes, extracellular vesicles generated by all cells, are naturally present in the blood. Here we demonstrate that enhanced retention of exosomes in circulation, compared to liposomes, is due to CD47 mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry siRNA or shRNA specific to oncogenic KRASG12D (iExosomes), a common mutation in pancreatic cancer. Compared to liposomes, iExosomes target oncogenic Kras with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. iExosomes treatment suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased their overall survival. Our results inform on a novel approach for direct and specific targeting of oncogenic Kras in tumors using iExosomes.

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miRTarBase 2020: updates to the experimentally validated microRNA–target interaction database

Hsi-Yuan Huang, Yang-Chi-Dung Lin, Jing. Li … (2019)

Abstract MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

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Author and article information

Contributors

Ning Wang: ningwang23@whut.edu.cn

Zengwu Shao: szwpro@163.com

Journal

Journal ID (nlm-ta): J Nanobiotechnology

Journal ID (iso-abbrev): J Nanobiotechnology

Title: Journal of Nanobiotechnology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-3155

Publication date (Electronic): 28 June 2022

Publication date PMC-release: 28 June 2022

Publication date Collection: 2022

Volume: 20

Electronic Location Identifier: 309

Affiliations

[1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Orthopeadics, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430022 Hubei China

[2 ]GRID grid.162110.5, ISNI 0000 0000 9291 3229, National Engineering Research Center of Fiber Optic Sensing Technology and Networks, , Wuhan University of Technology, ; Wuhan, 430070 China

Article

Publisher ID: 1516

DOI: 10.1186/s12951-022-01516-4

PMC ID: 9238182

SO-VID: 5da199fc-2f18-47f1-9f9c-cbc550e75e6e

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 18 April 2022

Date accepted : 18 June 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81802137

Award Recipient : Xi Chen

Funded by: FundRef http://dx.doi.org/10.13039/501100002858, China Postdoctoral Science Foundation;

Award ID: 2020M670029ZX

Award Recipient : Xi Chen

Custom metadata

ScienceOpen disciplines: Biotechnology

Keywords: diabetic wound,mir-21-5p,pvt1,graphene oxide,pdlla-peg-pdlla

Data availability:

ScienceOpen disciplines: Biotechnology

Keywords: diabetic wound, mir-21-5p, pvt1, graphene oxide, pdlla-peg-pdlla

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MiR-21 regulating PVT1/PTEN/IL-17 axis towards the treatment of infectious diabetic wound healing by modified GO-derived biomaterial in mouse models

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Abstract

Background

Method

Result

Conclusion

Supplementary Information

Related collections

Genome Engineering using CRISPR

Most cited references 58

The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses.

Exosomes Facilitate Therapeutic Targeting of Oncogenic Kras in Pancreatic Cancer

miRTarBase 2020: updates to the experimentally validated microRNA–target interaction database

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Cited by 7

Most referenced authors 9,622