ArticleCell death & disease2019
FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- [Role and mechanism of infrared thermography in early identification of necrosis risk in random-pattern flaps of mice].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Article
- 3,4-Dimethoxychalcone-induced caloric restriction inhibits PANoptosis to promote ischemic and diabetic skin flap survival: experimental studies.International journal of surgery (London, England) · 2026Article
- Functions of FGF21 and its role in cardiac hypertrophy.Journal of advanced research · 2026Review
- Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway.Cell regeneration (London, England) · 2025Article
- Allicin-loaded hydrogel enhances the viability of multiterritory perforator flap.Materials today. Bio · 2025Article
- Genetically-engineered Salmonella typhimurium expressing FGF21 promotes neurological recovery in ischemic stroke via FGFR1/AMPK/mTOR pathway.Journal of neuroinflammation · 2025Article
- 20-Deoxyingenol Activates Mitophagy Through TFEB and Promotes Functional Recovery After Spinal Cord Injury.Molecular neurobiology · 2025Article
- Melatonin enhances the viability of random-pattern skin flaps by activating the NRF2 pathway.Archives of medical science : AMS · 2025Article
- Dietary nitrate maintains homeostasis of oxidative stress and gut microbiota to promote flap survival in type 2 diabetes mellitus rats.BMC endocrine disorders · 2024Article
- Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.Autophagy · 2024Article
- FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases.Genes & diseases · 2024Review
- FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity.Autophagy · 2024Article
- Neuregulin-1, a member of the epidermal growth factor family, mitigates STING-mediated pyroptosis and necroptosis in ischaemic flaps.Burns & trauma · 2024Article
- FGF21 alleviates endothelial mitochondrial damage and prevents BBB from disruption after intracranial hemorrhage through a mechanism involving SIRT6.Molecular medicine (Cambridge, Mass.) · 2023Article
- RhFGF21 Protects Epidermal Cells against UVB-Induced Apoptosis through Activating AMPK-Mediated Autophagy.International journal of molecular sciences · 2022Article
- FGF21 alleviates microvascular damage following limb ischemia/reperfusion injury by TFEB-mediated autophagy enhancement and anti-oxidative response.Signal transduction and targeted therapy · 2022Article
- Inhibition of PLA2G4E/cPLA2 promotes survival of random skin flaps by alleviating Lysosomal membrane permeabilization-Induced necroptosis.Autophagy · 2022Article
- [Progress and thoughts on the regulation of wound repair by growth factors].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Article
- Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival.Communications biology · 2022Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21's therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.
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