Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT

Wu, Xue; Wang, Zheng; Wu, Gaofeng; Xu, Xichen; Zhang, Jian; Li, Yan; Zhang, Hong; Guo, Shuzhen

doi:10.3389/fphar.2020.00602

Cited by 15 publications

(7 citation statements)

References 28 publications

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“…Overall, the F2 hydrogel did not cause a toxic effect to the cells and allowed the cell attachment and proliferation. As a contrast, F2 hydrogel induced ~ 18% more early apoptosis, which might be an advantage and strategy for anti-scarring through reducing and "controlling" the surrounding number of fibroblasts [55][56][57] . However, this effect needs to be further investigated to understand the source and mechanism of causing early apoptosis fully.…”

Section: Resultsmentioning

confidence: 95%

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

Chun

Yap

Seet

et al. 2021

Sci Rep

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Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.

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Section: Resultsmentioning

confidence: 95%

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

Chun

Yap

Seet

et al. 2021

Sci Rep

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“…For each patient, the nature of the HS was established by three clinicians. HFBs were isolated according to previous methods [ 47 ]. NFBs were isolated from skin biopsy samples as previously described.…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis

et al. 2023

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Background Hypertrophic scars (HS) affect millions of people each year and require better treatment strategies. Bacterial extracellular vesicles (EVs) are advantaged by low cost and high yield which was commonly used in the treatment of diseases. Here, we investigated the therapeutic efficacy of EVs obtained from Lactobacillus druckerii in hypertrophic scar. In vitro, the effects of Lactobacillus druckerii-derived EVs (LDEVs) on Collagen I/III and α-SMA in fibroblasts obtained from HS. In vivo, a scleroderma mouse model was used to investigate the effects of LDEVs on fibrosis. The impact of LDEVs on excisional wound healing was explored. The different proteins between PBS and LDEVs treated fibroblasts derived from hypertrophic scar were studied by untargeted proteomic analysis. Results In vitro, LDEVs treatment significantly inhibited the expression of Collagen I/III and α-SMA and cell proliferation of fibroblasts derived from HS. In vivo, LDEVs withdrawn the hypertrophic scar formation in scleroderma mouse model and decreased the expression of α-SMA. LDEVs promoted the proliferation of skin cells, new blood vessel formation and wound healing in excisional wound healing mice model. Moreover, proteomics has shown that LDEVs inhibit hypertrophic scar fibrosis through multiple pathways. Conclusions Our results indicated that Lactobacillus druckerii-derived EVs has the potential application in the treatment of hypertrophic scars and any other fibrosis diseases. Graphical Abstract

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“…In-vitro studies have found that oxymatrine reduced the activity and collagen metabolism of human scar fibroblasts, increased cell apoptosis, and reduced the scar area and thickness ( Deng et al, 2021 ). Tetramethylpyrazine, the primary chemical component of Conioselinum anthriscoides “Chuanxiong” down-regulated fibrosis-related molecules (type I collagen, type III collagen, and α-SMA) to inhibit the proliferation of scar fibroblasts and activated the expression of Bax and Cleaved Caspase-3, which finally promoted the repair of HS( Wu et al, 2020 ). Besides, resveratrol inhibited HS formation by activating autophagy in HS fibroblasts via the miR-4654/Rheb axis ( Pang et al, 2020 ).…”

Section: The Hs Inhibitory Mechanism Of Tcmmentioning

confidence: 99%

Traditional Chinese medicine for hypertrophic scars—A review of the therapeutic methods and potential effects

Chen

Zhang

et al. 2022

Front. Pharmacol.

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Hypertrophic scar (HS) is a typical pathological response during skin injury, which can lead to pain, itching, and contracture in patients and even affect their physical and mental health. The complexity of the wound healing process leads to the formation of HS affected by many factors. Several treatments are available for HS, whereas some have more adverse reactions and can even cause new injuries with exacerbated scarring. Traditional Chinese Medicine (TCM) has a rich source, and most botanical drugs have few side effects, providing new ideas and methods for treating HS. This paper reviews the formation process of HS, the therapeutic strategy for HS, the research progress of TCM with its relevant mechanisms in the treatment of HS, and the related new drug delivery system of TCM, aiming to provide ideas for further research of botanical compounds in the treatment of HS, to promote the discovery of more efficient botanical candidates for the clinical treatment of HS, to accelerate the development of the new drug delivery system and the final clinical application, and at the same time, to promote the research on the anti-HS mechanism of multiherbal preparations (Fufang), to continuously improve the quality control and safety and effectiveness of anti-HS botanical drugs in clinical application.

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Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT

Cited by 15 publications

References 28 publications

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis

Traditional Chinese medicine for hypertrophic scars—A review of the therapeutic methods and potential effects

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