Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model

Gong, Yongfang; Zhang, Xiaoming; Liu, Fei; Wang, Zhenzhen; Deng, Xuefei; Jiao, Yi; Li, Xiaojing; Huang, Xueying

doi:10.1016/j.ejphar.2016.09.034

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…24,[55][56][57] Some studies demonstrate that the reduction in the hypertrophic scar is associated with a decrease in angiogenesis, and a few have directly explored the use of antiangiogenic therapies, including anti-VEGF and endostatin, to reduce scar formation in the rabbit model. [58][59][60] Together with the current study, then, a growing body of data supports the concept that robust angiogenesis spurs fibrosis in skin wounds, and that inhibition of angiogenesis, at least with the subgroup of agents that decreases VEGF activity, can reduce scar formation.…”

Section: Discussionsupporting

confidence: 76%

Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

Chen

Shi

et al. 2020

Wound Repair Regeneration

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Scar forming wounds are often characterized by higher levels of vascularity than non‐scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause‐effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full‐thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post‐wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF‐A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium‐derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post‐wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF‐335). rPEDF and PEDF‐335 were administered intradermally from day 4 post‐wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF‐335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF‐335, as a potential new strategy for the prevention or treatment of HSs.

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Section: Discussionsupporting

confidence: 76%

Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

Chen

Shi

et al. 2020

Wound Repair Regeneration

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“…This process is associated with the functions of various cells, such as fibroblasts, endothelial cells, macrophages and lymphocytes [ 15 , 16 , 17 ], among which the biological behavior of fibroblasts is considered to be a key factor in the scar formation process. Numerous studies have shown that fibroblasts, which happen to be the main constituents of keloid tissue, have the ability to over proliferate and are accompanied by incomplete apoptosis, together with the abnormal synthesis of collagen, which overall results in the continuous proliferation of keloid tissue [ 18 , 19 ]. Therefore, the inhibition of fibroblast proliferation and induction of apoptosis in keloid tissues can majorly reduce keloid tissue proliferation and thereby delay disease progression, which is important for the improvement and treatment of keloid scars.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

Yan

Nada

et al. 2021

Cells

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Objective: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. Methods: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. Results: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-β1 and TGF-β2) in HKFs and KNFs (p < 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p < 0.05). Conclusions: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs’ co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.

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“…Moreover, it also can inhibit the endothelial cell proliferation through competing with fibroblast growth factor, stopping phase G0/G1 transforming to phase S of cell cycle and in many other ways, as a result there'll be change in cell signaling pathway and can effectively inhibit the growth of multiple primary solid tumors as well as tumors which were metastasis. The expression and the function of multiple cytokines required by the growth of tumor cell also depend on NF-κB (30). The growth factor, EGF can activate NF-κB to cause the growth of solid tumor.…”

Section: Discussionmentioning

confidence: 99%

β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine inï¿½vitro and inï¿½vivo

et al. 2018

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Abstract. The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine in vitro as well as in in vivo. Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%). Furthermore, β-elemene-ligustrazine combination treatment resulted in the highest downregulation of G protein-coupled receptor 124, vascular endothelial growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein expression levels. In addition, the combined treatment led to an increase in the mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 in OS-732 cells. Additionally, β-elemene-ligustrazine caused a decrease in nuclear factor-κB, interleukin-8, C-X-C motif chemokine receptor 4 and urokinase-type plasminogen activator mRNA expression, as well as an increase in caspase-3, caspase-8, and caspase-9 mRNA expression. In vivo, the β-elemene-ligustrazine combination was able to reduce the weight and the bulk of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the results described above regarding changes to mRNA and protein expression were further confirmed in vivo in the tumor tissue of mice. The results of the present study have suggested that the combination of β-elemene-ligustrazine exhibits greater anticancer effects compared with β-elemeneor ligustrazine-alone treatment.

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Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model

Cited by 20 publications

References 37 publications

Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts

β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine inï¿½vitro and inï¿½vivo

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