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Surface refined Au^Quercetin nanoconjugate stimulates dermal cell migration: possible implication in wound healing.

ABSTRACT: Refining nutraceutical conjugated metal nanoparticles (NPs) and understanding their interactions with the cellular micro-environment is necessary for their application in nanomedicine. In the present experiment, we studied the effect of quercetin functionalized gold nanoparticles (Au^QurNP) on skin fibroblast and keratinocyte cell migration. Spherical shaped Au^QurNPs of 47 nm in size were formed due to the interaction of hydroxyl and carbonyl groups of quercetin with Au atoms as revealed by incremental algorithm-based analysis. Au^QurNP containing up to 5 μg l^-1 of Au with quercetin (5.2 ± 1.6 ng ml^-1) was least toxic to fibroblasts. Au^QurNP effectively reduced the generation of intracellular ROS (up to 63%) through free-radical scavenging activity. Au^QurNP also enhanced the rate of migration of fibroblasts (24 h) and keratinocytes (20 h) in artificially created wounds. The rate of migration of the cells towards the wound edge was in the order of Au^QurNP > control > quercetin > AuNP. Au^QurNP also significantly increased the expression of TGFβ1 protein, thereby inducing the downstream SMAD complex (SMAD 2-4). Downregulation of the inhibitory protein SMAD 7 by Au^QurNP helped in the nuclear translocation of SMADs 3 and 4. Collectively, the present in vitro study demonstrates the action of Au^QurNP on the SMAD family and the interconnected molecular mechanism leading to the cell migration process.

SUBMITTER: H M

PROVIDER: S-EPMC9057138 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Surface refined AuQuercetin nanoconjugate stimulates dermal cell migration: possible implication in wound healing.

H Madhyastha M S Halder H N Queen Intan QI R Madhyastha M A Mohanapriya M R Sudhakaran S L S Sajitha S K Banerjee B P Bethasiwi B H Daima D P N Navya N M Maruyama M Y Nakajima N

RSC advances 20201013 62

Refining nutraceutical conjugated metal nanoparticles (NPs) and understanding their interactions with the cellular micro-environment is necessary for their application in nanomedicine. In the present experiment, we studied the effect of quercetin functionalized gold nanoparticles (AuQurNP) on skin fibroblast and keratinocyte cell migration. Spherical shaped AuQurNPs of 47 nm in size were formed due to the interaction of hydroxyl and carbonyl groups of quercetin with Au atom ...[more]

PMID: 35515178

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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.

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Surface refined Au^Quercetin nanoconjugate stimulates dermal cell migration: possible implication in wound healing.

Publications

Surface refined Au<sup>Quercetin</sup> nanoconjugate stimulates dermal cell migration: possible implication in wound healing.

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