Liraglutide, a TFEB‐Mediated Autophagy Agonist, Promotes the Viability of Random‐Pattern Skin Flaps

Zhu, Xuwei; Hu, Xinli; Lou, Junsheng; Li, Jiafeng; Xu, Yu; Yu, Gaoxiang; Wu, Chen‐Yu; Ding, Jian; Gao, Weiyang; Xiao, Jian; Zhou, Kailiang; Jia, Chang

doi:10.1155/2021/6610603

Cited by 15 publications

(11 citation statements)

References 66 publications

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“…Therefore, autophagy is a double-edged sword and may play different roles in different diseases and disease progress ( Wang et al, 2021 ). Our previous studies have also shown that the effect of autophagy on flap viability is controversial and needs further research ( Li et al, 2020 ; Zhang et al, 2020 ; Chen et al, 2021 ; Zhu et al, 2021 ; Lou et al, 2022 ). Therefore, the present study seeks to explore the effects of DATS and DATS-induced autophagy on the survival of perforator flaps and to reveal its possible regulatory mechanisms.…”

Section: Introductionmentioning

confidence: 95%

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

et al. 2022

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The multiterritory perforator flap is one of the widest flap patterns used to repair tissue defects. However, flap necrosis of the distal part is still a challenging issue for plastic surgeons. Diallyl trisulfide (DATS) is an efficient ingredient extracted from garlic, exerting many important effects on different diseases. Our experiment aims to reveal whether DATS has a beneficial effect on the survival of perforator flaps and to explore its mechanism of action. The results showed that DATS enhanced angiogenesis and autophagy and reduced cell apoptosis and oxidative stress, thereby improving the survival rate of skin flaps. After co-administration with autophagy inhibitor 3-methyladenine (3MA), perforator flap survival was further improved. Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.

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Section: Introductionmentioning

confidence: 95%

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

et al. 2022

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“…Therefore, mediating autophagy is a method to promote the survival of random skin flaps, which has been supported by previous studies. 17,18 As a classical oxygen radicals scavenger, EDA has also been confirmed to possess the capability to mediate autophagy. Hence, we performed studies in vivo and vitro to investigate the role of EDA in promoting the survival of random skin flaps and its autophagy-related mechanisms (Figure 14).…”

Section: Discussionmentioning

confidence: 99%

“…43 Subsequently, Cleaved-Caspase3 is released from the damaged mitochondria and acted as an apoptotic executor in apoptosis. 18 Bcl-2 is a type of anti-apoptosis protein and prevents apoptosis from such mechanisms as inhibiting the function of proapoptotic gene p53, controling transcription factors and regulating the permeabilization of MOM. 44 Taken together, we found that the administration of EDA alleviated apoptosis of random skin flaps and MUVECs.…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy is a significant cellular organelle and macromolecular materials degradation process for regulating cellular signalling, maintaining cellular homeostasis, and promoting cell survival in the pathological environments such as ischemia, oxygen deficiency, inflammation and oxidative stress et al 14,15 Many studies had found that mediating autophagy could promote the survival of random skin flaps. [16][17][18] However, when ischemia occurs, the roles and changes in autophagy in survival zones, intermediate zones and necrosis zones are still unknown. In survival zones, autophagy is maintained at the normal level to ensure the proper function of metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Qin

Zhao³

et al. 2023

International Wound Journal

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Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia–reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy‐related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3‐methyladenine (3‐MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3‐MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA‐induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.

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“…Acacetin was reported to activate TFEB independent of the mTOR signaling pathway [112]. Furthermore, AMPK activation by PNU-282987, liraglutide and metformin induces mTOR inhibition and enhances TFEB-mediated lysosomal biogenesis and autophagy [113][114][115][116].…”

Section: Therapeutic Potential Of Targeting Tfeb In Neurodegenerative...mentioning

confidence: 99%

Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer’s Disease and Parkinson’s Disease

Yang¹,

Zhang²,

Zhang³

et al. 2023

Aging and disease

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A key pathological feature of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is the accumulation of aggregated and misfolded protein aggregates with limited effective therapeutic agents. TFEB (transcription factor EB), a key regulator of lysosomal biogenesis and autophagy, plays a pivotal role in the degradation of protein aggregates and has thus been regarded as a promising therapeutic target for these NDs. Here, we systematically summarize the molecular mechanisms and function of TFEB regulation. We then discuss the roles of TFEB and autophagy-lysosome pathways in major neurodegenerative diseases including AD and PD. Finally, we illustrate small molecule TFEB activators with protective roles in NDs animal models, which show great potential for being further developed into novel antineurodegenerative agents. Overall, targeting TFEB for enhancing lysosomal biogenesis and autophagy may represent a promising opportunity for the discovery of disease-modifying therapeutics for neurodegenerative disorders though more in-depth basic and clinical studies are required in the future.

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Liraglutide, a TFEB‐Mediated Autophagy Agonist, Promotes the Viability of Random‐Pattern Skin Flaps

Cited by 15 publications

References 66 publications

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer’s Disease and Parkinson’s Disease

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