Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival

Chen, Zhengtai; Zhang, Chenxi; Ma, Haiwei; Huang, Zihuai; Li, Jiafeng; Lou, Junshen; Li, Baolong; Tu, Qiuyun; Gao, Weiyang

doi:10.3389/fphar.2020.00951

Cited by 20 publications

(7 citation statements)

References 54 publications

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“…Before the operation, the rat dorsal midline was used as the medial border of the flap. The pedicle was located on the unilateral deep circumflex iliac (DCI) artery to establish a right-side perforator flap (2.5 × 11 cm 2 ) in every rat as reported previously ( Chen et al, 2020 ) ( Figure 1A ). After the flaps were completely lifted from the underlying fascia, a satisfactory hemostatic effect was obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting analysis of proteins in flap tissue was conducted as described previously ( Chen et al, 2020 ), including the following proteins: VEGF (1:1,000, ProteinTech), Cadherin 5 (1:1,000, Affinity), LC3II (1:500, ProteinTech), SOD1 (1:1,000, ProteinTech), C-CASP3 (1:1,000, CST), MMP9 (1:1,000, Abcam), SQSTM1/p62 (1:1,000, Abcam), Bax (1:1,000, ProteinTech), CTSD (1:1,000, ABclonal), HO-1 (1:1,000, ProteinTech), Bcl-2 (1:1,000, CST), eNOS (1:1,000, Abcam), VPS34 (1:1,000, ProteinTech), Beclin1 (1:1,000, ProteinTech), PI3K (1:1,000, ProteinTech), AKT (1:1,000, ProteinTech), p-PI3K (1:1,000, CST), p -Akt (1:1,000, CST), AMPK (1:1,000, CST), p -AMPK (1:1,000, CST), HIF-1α (1:1,000, Abcam), and GAPDH (1:1,000, ProteinTech). Finally, the intensity of Western blotting was quantified using Image Lab 3.0 software (Bio-Rad, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

et al. 2022

Self Cite

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“…Therefore, modulation of autophagy may be a mechanism that could be used to treat diseases related to inflammation [ 42 ]. Recent studies reported that DPP4 inhibitors increase autophagy [ 28 , 43 ]. In the current study, both LC3 II and p62 levels were increased by evogliptin, and evogliptin consequently increased autophagy flux.…”

Section: Discussionmentioning

confidence: 99%

Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells

Seo

Lee

Han

et al. 2022

IJMS

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Chronic liver inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Kupffer cells (KC) secrete proinflammatory and fibrogenic cytokines in response to lipopolysaccharide (LPS), and so play an important role in liver inflammation, where they induce hepatocellular damage. LPS also activates hepatic stellate cells and induces extracellular matrix deposition. In this study, we used isolated primary KC, primary hepatocytes, and primary hepatic stellate cells (HSC) to investigate whether evogliptin directly inhibits inflammatory and fibrotic signaling. We found that evogliptin inhibited LPS-induced secretion of inducible nitric oxide synthase and transforming growth factor β (TGF-β) from KC. Moreover, evogliptin inhibited inflammatory mediator release from hepatocytes and hepatic stellate cell activation that were induced by KC-secreted cytokines. In hepatocytes, evogliptin also inhibited LPS-induced expression of proinflammatory cytokines and fibrotic TGF-β. In addition, evogliptin inhibited TGF-β-induced increases in connective tissue growth factor levels and HSC activation. These findings indicate that evogliptin inhibits inflammatory and fibrotic signaling in liver cells. We also showed that the inhibitory effect of evogliptin on inflammatory and fibrotic signaling is associated with the induction of autophagy.

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“…Then, after dehydrating the flap in an autoclave until the weight remained consistent for 2 days, the flaps were weighed according to their BA dry weight. The edema ratio is (wet weight À dry weight)/wet weight 100% (Chen et al, 2020).…”

Section: Assessment Of Flap Survival Area and Edemamentioning

confidence: 99%

Baicalin promotes random‐pattern skin flap survival by inducing autophagy via AMPK‐regulated TFEB nuclear transcription

Zhang

et al. 2023

Phytotherapy Research

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The random‐pattern skin flap is a generally used technique to cover the soft tissue defect, while its application is often constrained by complications after the flap transplant. Necrosis of the flap remains a principal obstacle. The purpose of this study was to investigate the effect of Baicalin on skin flap survival and its mechanism. First of all, we discovered that administering Baicalin stimulated cell migration and boosted the formation of capillary tubes in human umbilical vein endothelial cells. Then, we detected that Baicalin reduced apoptosis‐induced oxidative stress by using western blot and oxidative stress test kit. After that, we observed that Baicalin increased autophagy and utilized 3MA to block autophagy augmentation substantially reversing the effects of Baicalin therapy. Furthermore, we uncovered the underlying mechanisms of Baicalin‐induced autophagy via AMPK‐regulated TFEB nuclear transcription. Finally, our in vivo experiment findings showed that Baicalin reduces oxidative stress, inhibits apoptosis, promotes angiogenesis, and boosts the levels of autophagy. After autophagy was blocked, substantially reversing the effects of Baicalin therapy. Our study indicated that Baicalin‐induced autophagy via AMPK regulated TFEB nuclear transcription and then promotes angiogenesis and against oxidative stress and apoptotic promotes skin flap survival. These findings highlight the therapeutic potential for the clinical application of Baicalin in the future.

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Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival

Cited by 20 publications

References 54 publications

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps

Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells

Baicalin promotes random‐pattern skin flap survival by inducing autophagy via AMPK‐regulated TFEB nuclear transcription

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