Dataset Information

Porous Se@SiO₂ Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

ABSTRACT: Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO₂ nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization, antioxidant capacity and biological safety of Se@SiO₂ NPs were evaluated. A full-thickness excisional wound model was established, and the wounds were divided into three groups. The re-epithelization and distribution of collagen fibers were assessed using hematoxylin and eosin staining and Masson's trichome staining after specific treatments. Our results revealed that the Se@SiO₂ NPs accelerated dermal wound healing and suppressed the formation of hypertrophic scars, accompanied by oxidative stress inhibition. Moreover, we found that Se@SiO₂ NPs worked by activating the PI3K/Akt pathway and upregulating the phosphorylation of Akt. The findings of our study provide a new method to promote dermal scar-free wound healing by suppressing excessive oxidative stress and through PI3K/Akt pathway activation.

SUBMITTER: Yang BY

PROVIDER: S-EPMC8978548 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Porous Se@SiO<sub>2</sub> Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Yang Bo-Yu BY Zhou Zhi-Yuan ZY Liu Shi-Yun SY Shi Ming-Jun MJ Liu Xi-Jian XJ Cheng Tian-Ming TM Deng Guo-Ying GY Tian Ye Y Song Jian J Li Xuan-Hao XH

Frontiers in bioengineering and biotechnology 20220321

Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO<sub>2</sub> nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization ...[more]

PMID: 35387298

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Project description:BackgroundLipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects.MethodsThe effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1β of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1β, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs).ResultsThe porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1β, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs.ConclusionPorous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.

Project description:BackgroundFoxn1-/- deficient mice are a rare model of regenerative skin wound healing among mammals. In wounded skin, the transcription factor Foxn1 interacting with hypoxia-regulated factors affects re-epithelialization, epithelial-mesenchymal transition (EMT) and dermal white adipose tissue (dWAT) reestablishment and is thus a factor regulating scar-forming/reparative healing. Here, we hypothesized that transcriptional crosstalk between Foxn1 and Hif-1α controls the switch from scarless (regenerative) to scar-present (reparative) skin wound healing. To verify this hypothesis, we examined (i) the effect of hypoxia/normoxia and Foxn1 signalling on the proteomic signature of Foxn1-/- (regenerative) dermal fibroblasts (DFs) and then (ii) explored the effect of Hif-1α or Foxn1/Hif-1α introduced by a lentiviral (LV) delivery vector to injured skin of regenerative Foxn1-/- mice with particular attention to the remodelling phase of healing.ResultsWe showed that hypoxic conditions and Foxn1 stimulation modified the proteome of Foxn1-/- DFs. Hypoxic conditions upregulated DF protein profiles, particularly those related to extracellular matrix (ECM) composition: plasminogen activator inhibitor-1 (Pai-1), Sdc4, Plod2, Plod1, Lox, Loxl2, Itga2, Vldlr, Ftl1, Vegfa, Hmox1, Fth1, and F3. We found that Pai-1 was stimulated by hypoxic conditions in regenerative Foxn1-/- DFs but was released by DFs to the culture media exclusively upon hypoxia and Foxn1 stimulation. We also found higher levels of Pai-1 protein in DFs isolated from Foxn1+/+ mice (reparative/scar-forming) than in DFs isolated from Foxn1-/- (regenerative/scarless) mice and triggered by injury increase in Foxn1 and Pai-1 protein in the skin of mice with active Foxn1 (Foxn1+/+ mice). Then, we demonstrated that the introduction of Foxn1 and Hif-1α via lentiviral injection into the wounded skin of regenerative Foxn1-/- mice activates reparative/scar-forming healing by increasing the wounded skin area and decreasing hyaluronic acid deposition and the collagen type III to I ratio. We also identified a stimulatory effect of LV-Foxn1 + LV-Hif-1α injection in the wounded skin of Foxn1-/- mice on Pai-1 protein levels.ConclusionsThe present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1-/- DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1-/- mice activates reparative/scar-forming healing.

Dataset Information

Porous Se@SiO₂ Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Publications

Porous Se@SiO<sub>2</sub> Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

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Dataset Information

Porous Se@SiO2 Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Publications

Porous Se@SiO<sub>2</sub> Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Porous Se@SiO₂ Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.