Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

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Abstract

Gelatine nanostructured lipid carriers (GNLs) have attracted increasing attention due to their biodegradable status and capacity to capture various biologically active compounds. Many studies demonstrated that fibroblast growth factor therapies after spinal cord injury (SCI) can be used in the future for the recovery of neurons. In this study, the therapeutic effects of GNL-encapsulated fibroblast growth factor 15 (FGF15) and FGF15 were compared in SCI. The FGF15-GNLs had 88.17 ± 1.22% encapsulation efficiency and 4.82 ± 0.12% loading capacity. The effects of FGF15-GNLs and FGF15 were assessed based on the Basso–Beattie–Bresnahan (BBB) locomotion scale, inclined plane test and footprint analysis. Immunofluorescent staining was used to identify the expression of autophagy-associated proteins, GFAP (glial fibrillary acidic protein) and neurofilament 200 (NF200). FGF15-GNLs use enhanced the repair after SCI compared to the effect of FGF15. The suppression of autophagy-associated proteins LC3-II and beclin-1, and p62 enhancement by FGF15-GNLs treatment were more pronounced. Thus, the effects of FGF15-GNLs on the recovery after SCI are related to the inhibition of autophagy and glial scar, and promotion of nerve regeneration in SCI.

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Most cited references 45

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Mechanism and medical implications of mammalian autophagy

Zvulun Elazar, Ivan Dikic (2018)

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Cell death: a review of the major forms of apoptosis, necrosis and autophagy

Mark D’Arcy (2019)

Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.

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Role of hypoxia in cancer therapy by regulating the tumor microenvironment

Xinming Jing, Fengming Yang, Chuchu Shao … (2019)

Aim Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. Methods Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms. Results Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux. Conclusion Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.

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Author and article information

Contributors

Haicheng Dou: haichengdou@wzhealth.com

Sunren Sheng: shengsunren82330@126.com

Sipin Zhu: sipinzhu@163.com

Journal

Journal ID (nlm-ta): Cell Death Discov

Journal ID (iso-abbrev): Cell Death Discov

Title: Cell Death Discovery

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2058-7716

Publication date (Electronic): 2 December 2020

Publication date PMC-release: 2 December 2020

Publication date Collection: 2020

Volume: 6

Electronic Location Identifier: 137

Affiliations

[1 ]GRID grid.417384.d, ISNI 0000 0004 1764 2632, Department of Orthopaedics, , The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, ; Wenzhou, Zhejiang 325000 China

[2 ]GRID grid.268099.c, ISNI 0000 0001 0348 3990, The Second School of Medicine, , Wenzhou Medical University, ; Wenzhou, 325027 China

Article

Publisher ID: 367

DOI: 10.1038/s41420-020-00367-y

PMC ID: 7710748

SO-VID: 32655856-f7cc-4e4f-af50-cf8be2ca1894

License:

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 5 August 2020

Date revision received : 12 October 2020

Date accepted : 27 October 2020

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 81802235

Award Recipient : Sipin Zhu

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Keywords: neuroscience,physiology

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Keywords: neuroscience, physiology

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Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury

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Karger: Neurology and Neuroscience

Most cited references 45

Mechanism and medical implications of mammalian autophagy

Cell death: a review of the major forms of apoptosis, necrosis and autophagy

Role of hypoxia in cancer therapy by regulating the tumor microenvironment

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