Filaggrin and beyond

Stefanovic, Nicholas; Irvine, Alan D.

doi:10.1016/j.anai.2023.09.009

Cited by 12 publications

(3 citation statements)

References 128 publications

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“…This aligns with previous studies linking reduced concentration of structural proteins like keratins and filaggrin to compromised skin barrier function [41][42][43][44]. Filaggrin is one of the key structural proteins essential for the adhesion and mechanical functions of corneocytes in maintaining skin barrier function [45]. We noted that TOP application of filaggrin monomers could restore the skin barrier in filaggrin-deficient flaky tail (ft/ft) mice [46], highlighting the potential of stratum corneum-like proteins in TOP MSC-sEVs to augment the skin barrier.…”

Section: Discussionsupporting

confidence: 90%

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy

Zhang,

Lai,

Sim

et al. 2024

Biomolecules

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Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness. All three routes of administration significantly reduced BLM-induced fibrosis in the skin, as determined by Masson’s Trichrome staining. However, only TOP administration reduced BLM-induced dermal collagen density, with no effect on dermal thickness observed for all administration routes. Moreover, SC, but not TOP or IP administration, increased anti-inflammatory profibrotic CD163+ M2 macrophages. These findings indicate that the administration route influences the therapeutic efficacy of MSC-sEVs in alleviating dermal fibrosis, with TOP administration being the most effective, and this efficacy is not mediated by M2 macrophages. Since both TOP and SC administration target the skin, the difference in their efficacy likely stems from variations in MSC-sEV delivery in the skin. Fluorescence-labelled TOP, but not SC MSC-sEVs when applied to skin explant cultures, localized in the stratum corneum. Hence, the superior efficacy of TOP over SC MSC-sEVs could be attributed to this localization. A comparison of the proteomes of stratum corneum and MSC-sEVs revealed the presence of >100 common proteins. Most of these proteins, such as filaggrin, were known to be crucial for maintaining skin barrier function against irritants and toxins, thereby mitigating inflammation-induced fibrosis. Therefore, the superior efficacy of TOP MSC-sEVs over SC and IP MSC-sEVs against SSc is mediated by the delivery of proteins to the stratum corneum to reinforce the skin barrier.

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Section: Discussionsupporting

confidence: 90%

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy

Zhang,

Lai,

Sim

et al. 2024

Biomolecules

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“…Filaggrin (FLG), a fundamental protein abundantly present in the epidermis, plays a crucial role in maintaining the skin's structure. Moreover, the breakdown products of silk broin demonstrate remarkable bene ts in terms of skin hydration, moisture retention, protection against UV radiation, regulation of cytokine production, and defense against bacterial invasion [8,9] . Aquaporin 3 (AQP3) is a crucial membrane transport protein that plays a signi cant role in the proliferation, differentiation, and migration of keratinocytes.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid combined with Centella asiatica extract improve skin barrier function and alleviate inflammatory damage via JAK/STAT3 signaling pathway

Shi,

Liu,

et al. 2024

Preprint

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Objective Psoriasis, as a chronic inflammatory skin disease, has complex pathogenesis, stubborn condition and high recurrence rate. Centella asiatica (L.) Urban (CA) is one of the commonly used Chinese herbal medicines in dermatology, which has multiple pharmacological activities such as promoting wound healing, anti-cell proliferation and anti-inflammation. Hyaluronic acid (HA) has become an excellent moisturizing ingredient and is widely used in skin care products. This study aims to explore the effects and mechanism of HA combined with CA on skin inflammatory injury and provide experimental basis for the future application research of HA and CA in inflammatory skin diseases. Methods In this study, the skin barrier repair function and the mechanisms of HA combined with CA were evaluated. The expressions of inflammatory factors and barrier related factors were detected in LPS-induced HaCaT cells. The effects on the migration and angiogenesis ability were analyzed in VEGF- induced HUVECs. Results HA with different molecular weights increased the contents of GSH and SOD in LPS-induced HaCaT cells, eliminated free radicals, reduced the production of ROS, and inhibited cell oxidative stress. Among them, HA with molecular weight of 6100Da was the best, followed by 1220KDa HA. It was found that the molecular weight of 1220KDa HA effectively inhibited IFN-γ mRNA level, increase the content of AQP3 and FLG in cells. Mechanism research showed that HA inhibited inflammation was related to block the transduction of NF-κB and JAK/STAT3 pathways. Meanwhile, 1220KDa HA (2 mg/mL) combined with ethyl acetate of CA (CAE, 25 µg/mL) could effectively inhibit the expression of MMP-1 in LPS-induced HaCaT cells, increase the expression of skin barrier related proteins AQP3 and FLG, and reduce the secretion of IL-17. HA combined with CAE enhanced the inhibition of NF-κB and JAK/STAT3 pathways, improving the inhibitory effects of CAE on IFN-γ and IL-6. In addition, after the intervention of HA combined with CAE, the migration and the angiogenesis abilities of VEGF-induced HUVEC cells were decreased. Conclusion HA combined with CAE can reduce release of inflammatory factors and improve the function of skin barrier via the inhibition of NF-κB and JAK/STAT3 pathways, alleviating psoriasis like inflammatory damage.

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“…The FLG gene contains 3 exons with most coding sequences localized to exon 3, a 12-kilobase segment containing 10-12 filaggrin repeats and other domains essential to filaggrin function in the skin (8). FLG loss-of-function (LoF) mutations, which result in nonfunctional filaggrin protein, are known to contribute to the skin barrier defect observed in many patients with AD (9). Studies estimate that 10%-40% of patients with AD have at least 1 FLG LoF variant, with incidence correlated with AD severity (10,11).…”

Section: Introductionmentioning

confidence: 99%

Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort

Virolainen,

Satish,

Biagini

et al. 2024

JCI Insight

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Filaggrin and beyond

Cited by 12 publications

References 128 publications

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy

Hyaluronic acid combined with Centella asiatica extract improve skin barrier function and alleviate inflammatory damage via JAK/STAT3 signaling pathway

Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort

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