Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model DOI Creative Commons
Xiao Guo,

Christoph Schaudinn,

Ulrike Blume‐Peytavi

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(7), P. 1198 - 1198

Published: April 2, 2022

Adult stem cells have been extensively investigated for tissue repair therapies. Adipose-derived (ASCs) were shown to improve wound healing by promoting re-epithelialization and vascularization as well modulating the inflammatory immune response. In this study, we used ex vivo human skin cultured in a six-well plate with trans-well inserts model superficial wounds. Standardized wounds created treated allogeneic ASCs, ASCs conditioned medium (ASC-CM), or cell culture (DMEM) supplemented fetal calf serum (FCS). Skin viability (XTT test), histology (hematoxylin eosin, H E), β-catenin expression mediators growth factors monitored over 12 days of culture. We observed only moderate time-dependent decrease metabolic activity while morphology was preserved, occurred at edges. An increase newly formed epithelia, especially samples ASC-CM. general, increased mediators, e.g., hepatocytes factor (HGF), platelet-derived subunit AA (PDGF-AA), IL-1α, IL-7, TNF-α, IL-10, incubation time. Interestingly, different profiles treatments. Samples ASC-CM significantly levels cytokines PDGF-AA respect control, whereas treatment DMEM 10% FCS resulted fibroblast factor-basic (FGF-basic) increases immunomodulatory cytokines. These results confirm that microenvironment can influence type secreted mode how they process. Comparative investigations pre-activated will elucidate further aspects mechanism protocols ACS application.

Language: Английский

The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds DOI Creative Commons
Tithi Roy, Samuel Boateng, Mohammad B. Uddin

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1671 - 1671

Published: June 20, 2023

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, vitiligo, is associated with poor treatment outcomes. Improved comprehension the consequences PI3K/Akt/mTOR patients resulted development novel therapeutic approaches. Nonetheless, more studies are necessary to validate regulatory role this create effective preventive methods for a wide range skin diseases. Several have revealed that certain natural products synthetic compounds can obstruct expression/activity PI3K/Akt/mTOR, underscoring their potential managing common persistent disorders. This review summarizes recent advances understanding activated components discusses bioactive products, scaffolds, biologic agents prevention treatment. However, further research develop therapies

Language: Английский

Citations

50
Metabolic reprogramming in skin wound healing DOI Creative Commons
Zitong Wang,

Feng Zhao,

Chengcheng Xu

et al.

Burns & Trauma, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 1, 2024

Abstract Metabolic reprogramming refers to the ability of a cell alter its metabolism in response different stimuli and forms pressure. It helps cells resist external stress provides them with new functions. Skin wound healing involves metabolic nutrients, such as glucose, lipids, amino acids, which play vital roles proliferation, differentiation, migration multiple types. During glucose process wounds, transporters key enzymes cause elevated metabolite levels. Glucose-mediated oxidative drives proinflammatory promotes healing. Reprogramming lipid increases number fibroblasts decreases macrophages. enhances local neovascularization improves fibrin stability promote extracellular matrix remodelling, accelerates healing, reduces scar formation. acid affects re-epithelialization, collagen deposition, angiogenesis. However, comprehensive reviews on role skin are lacking. Therefore, we have systematically reviewed acids during Notably, identified their targets potential therapeutic value elucidated mechanisms action.

Language: Английский

Citations

32
Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders DOI Creative Commons
Laura Mercurio, Cristina Albanesi, Stefania Madonna

et al.

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: April 30, 2021

PhosphoInositide-3 Kinase (PI3K) represents a family of different classes kinases which control multiple biological processes in mammalian cells, such as cell growth, proliferation, and survival. Class IA PI3Ks, the main regulators proliferative signals, consists catalytic subunit (α, β, δ) that binds p85 regulatory mediates activation AKT Target Of Rapamycin (mTOR) pathways regulation downstream effectors. Dysregulation PI3K/AKT/mTOR pathway skin contributes to several pathological conditions characterized by uncontrolled including cancers, psoriasis, atopic dermatitis (AD). Among cutaneous basal carcinoma (BCC) squamous (cSCC) display signaling hyperactivation, implicated hyperproliferation, tumorigenesis, well resistance apoptosis. Upregulation mTOR proteins has also been reported association with enhanced defective keratinocyte differentiation, senescence-like growth arrest, apoptosis, accounting for major parts overall disease phenotypes. On contrary, role AD is less characterized, even though recent evidence demonstrates relevant function epidermal barrier formation stratification. In this review, we provide most updates on molecular axis pathogenesis hyperproliferative disorders, highlights current status preclinical clinical studies PI3K-targeted therapies.

Language: Английский

Citations

70
The Relapse of Psoriasis: Mechanisms and Mysteries DOI Creative Commons
Danning Tian, Yuping Lai

JID Innovations, Journal Year: 2022, Volume and Issue: 2(3), P. 100116 - 100116

Published: March 9, 2022

Language: Английский

Citations

62
Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential DOI Open Access
Fani Karagianni, Antreas Pavlidis,

Lina S. Malakou

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1693 - 1693

Published: Feb. 1, 2022

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation cell proliferation, survival, and motility response to availability energy nutrients as well mitogens. mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, survival many tissues. In skin, dysregulation PI3K/AKT/mTOR pathway may lead severe pathological conditions characterized by uncontrolled proliferation inflammation, skin hyperproliferative malignant diseases. Herein, we provide an update on current knowledge regarding pathogenic implication diseases with inflammatory features (such psoriasis, atopic dermatitis, pemphigus, acne) characteristics cutaneous T lymphoma melanoma) while critically discuss future perspectives for therapeutic targeting clinical practice.

Language: Английский

Citations

54
Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors DOI Open Access
Wenge Zheng, Huijuan Li, Yuyo Go

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(21), P. 4588 - 4588

Published: Nov. 1, 2022

Our skin is an organ with the largest contact area between human body and external environment. Skin aging affected directly by both endogenous factors exogenous (e.g., UV exposure). saccharification, a non-enzymatic reaction proteins, e.g., dermal collagen naturally occurring reducing sugars, one of basic root causes aging. During reaction, series complicated glycation products produced at different stages pathways are usually collectively referred to as advanced end (AGEs). AGEs cause cellular dysfunction through modification intracellular molecules accumulate in tissues also associated variety age-related diseases, such diabetes, cardiovascular disease, renal failure (uremia), Alzheimer’s disease. age amplified factors, ultraviolet radiation, resulting wrinkles, loss elasticity, dull yellowing, other problems. This article focuses on damage mechanism glucose its summarizing biochemical characteristics, compositions, well processes production elimination AGEs. One important parts this would be summarize current inhibitors gain insight into anti-glycation development promising natural effects.

Language: Английский

Citations

45
Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation DOI Creative Commons
Tithi Roy,

Sergette Banang‐Mbeumi,

Samuel Boateng

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 18, 2023

Psoriasis is a chronic autoimmune inflammatory skin disorder characterized by epidermal hyperplasia and aberrant immune response. In addition to cytokine production, psoriasis associated with activation of the Akt/mTOR pathway. mTOR/S6K1 regulates T-lymphocyte migration, keratinocytes proliferation upregulated in psoriatic lesions. Several drugs that target Th1/Th17 cytokines or their receptors have been approved for treating humans variable results necessitating improved therapies. Fisetin, natural dietary polyphenol anti-oxidant anti-proliferative properties, covalently binds mTOR/S6K1. The effects fisetin on its underlying mechanisms not clearly defined. Here, we evaluated immunomodulatory Th1/Th17-cytokine-activated adult human (HEKa) anti-CD3/CD28-stimulated CD4 + T cells compared these activities those rapamycin (an mTOR inhibitor). Transcriptomic analysis HEKa revealed 12,713 differentially expressed genes (DEGs) fisetin-treated group 7,374 DEGs rapamycin-treated group, both individually treated group. Gene ontology enriched functional groups related PI3K/Akt/mTOR signaling pathways, psoriasis, development. Using silico molecular modeling, observed high binding affinity IL-17A. vitro , significantly inhibited activity, increased expression autophagy markers LC3A/B Atg5 suppressed secretion IL-17A activated lymphocytes co-cultured HEKa. Topical administration an imiquimod (IMQ)-induced mouse model exhibited better effect than reducing psoriasis-like inflammation phosphorylation promoting keratinocyte differentiation mice Fisetin also T-lymphocytes F4/80 macrophage infiltration into skin. We conclude potently inhibits pathway promotes alleviate IMQ-induced disease mice. Altogether, our findings suggest as potential treatment possibly other diseases.

Language: Английский

Citations

28
Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets DOI Creative Commons
Lisha Li, Jiaye Lu, Jun Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development psoriasis closely related to abnormal activation and disorders the immune system. Dysregulated skin protective mechanisms can activate pathways within epithelial microenvironment (EIME), leading autoimmune-related diseases. In this review, we initially emphasized pathogenesis psoriasis, paying particular attention interactions between cells production cytokines in psoriasis. Subsequently, delved into significance EIME emergence A thorough understanding these processes crucial targeted therapies for Finally, discussed potential novel aimed at modulating This comprehensive examination sheds light on intricate underlying provides insights therapeutic avenues immune-mediated

Language: Английский

Citations

15
Epidermal barrier impairment predisposes for excessive growth of the allergy‐associated yeast Malassezia on murine skin DOI Creative Commons
Fiorella Ruchti, Pascale Zwicky, Burkhard Becher

et al.

Allergy, Journal Year: 2024, Volume and Issue: 79(6), P. 1531 - 1547

Published: Feb. 22, 2024

Abstract Background The skin barrier is vital for protection against environmental threats including insults caused by skin‐resident microbes. Dysregulation of this a hallmark atopic dermatitis (AD) and ichthyosis, with variable consequences host immune control colonizing commensals opportunistic pathogens. While Malassezia the most abundant commensal fungus skin, little known about in inflammatory diseases. Methods In experimental study, MC903‐treated mice were colonized spp. to assess host–fungal interactions dermatitis. Additional murine models AD tape stripping, K5‐Nrf2 overexpression flaky tail mice, employed confirm expand findings. Skin fungal counts enumerated. High parameter flow cytometry was used characterize antifungal response AD‐like skin. Structural functional alterations determined histology transcriptomics bulk Finally, differential expression metabolic genes quantified. Results grows excessively Fungal overgrowth could, however, not be explained altered status Instead, we found that upregulating key cutaneous niche, acquired enhanced fitness efficiently colonise impaired barrier. Conclusions This study provides evidence structural changes dysfunctional epidermal environment provide increased accessibility an lipid profile, which lipid‐dependent yeast adapts nutrient assimilation. Our findings reveal fundamental insights into implication mycobiota pathogenesis common disorders.

Language: Английский

Citations

10
Metabolic rewiring of macrophages by epidermal-derived lactate promotes sterile inflammation in the murine skin DOI Creative Commons
Uttkarsh Ayyangar, Aneesh Karkhanis,

Heather Tay

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(7), P. 1113 - 1134

Published: Feb. 28, 2024

Abstract Dysregulated macrophage responses and changes in tissue metabolism are hallmarks of chronic inflammation the skin. However, metabolic cues that direct support functions skin poorly understood. Here, we show during sterile inflammation, epidermis macrophages uniquely depend on glycolysis TCA cycle, respectively. This compartmentalisation is initiated by ROS-induced HIF-1α stabilization leading to enhanced epidermis. The end-product glycolysis, lactate, then exported epithelial cells utilized dermal induce their M2-like fates through NF-κB pathway activation. In addition, psoriatic disorder also driven such lactate metabolite-mediated crosstalk between macrophages. Notably, small-molecule inhibitors transport this setting attenuate psoriasis disease burden, suppress fate acquisition Our study identifies an essential role for metabolite regulating which may be effectively targeted treat inflammatory disorders as psoriasis.

Language: Английский

Citations

10