Multitranscriptome analysis revealed that stromal cells in the papillary dermis promote angiogenesis in psoriasis vulgaris DOI Creative Commons
Bo Zhang, Junpu Mei, Qijun Liao

et al.

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Abstract Background The pathogenesis of psoriasis is incompletely understood. Growing evidence suggests the involvement stromal cells in inflammatory process. Objectives To investigate roles cells, including fibroblasts, vascular endothelial (VECs) and smooth muscle (VSMCs), psoriatic microenvironment, possible underlying mechanisms involved. Methods We used a combination single-cell, spatial transcriptome bulk RNA sequencing lesional nonlesional skin samples from patients with vulgaris (PV) healthy unaffected individuals. Results By analysing transcriptomes 364 098 single we uncovered WNT5A+ (Wnt-5a) ITIH5+ (inter-α-trypsin inhibitor heavy chain 5) VECs VCAN+ (versican) VSMCs, significantly increased proportions these papillary dermis skin. defined eight unique subclusters fibroblasts observed shift WIF1+ (Wnt inhibitory factor 1) toward abnormal activation noncanonical Wnt signalling pathway angiogenic proinflammatory capabilities. VSMCs were able to undergo phenotypic transformation contractile synthetic phenotype during development inflammation. found have an essential role regulating angiogenesis remodelling pathological changes seen PV. Ligand receptor analyses that are extensively implicated interactions various cell types, especially TIH5+ dermis. Conclusions Interactions identified as pathogenic elements Improving microenvironment by targeting might be potential treatment strategy

Language: Английский

Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis DOI Creative Commons
Yuchao Chen, Huazhen Liu, Yuming He

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 51 - 51

Published: Jan. 2, 2025

Psoriasis is a chronic, recurrent and inflammatory skin disease. Although conventional immunosuppressants can ameliorate psoriatic symptoms, it tends to relapse over time. Previous studies have shown that exosomes from both immune non-immune cells participate in immunopathology. The biologically active cargoes accelerate psoriasis progression by altering gene profiles signaling pathways of neighboring cells. On the other hand, be utilized as drug delivery platforms for treatment. Especially, engineered may serve systems effective proteins, nucleic acids or drugs due their low immunogenicity, good stability ability fuse with target Therefore, investigation into mechanisms underlying intercellular communications mediated lesions likely helps design therapy psoriasis. In this review, we summarized recent advances biogenesis potential roles pathogenesis treatment further discussed challenges future directions particular, review highlights immunoregulatory function derived exosome-based therapeutic applications psoriasis, including systems. Thus, help

Language: Английский

Citations

0
Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression DOI Creative Commons
Yuyu Zhu,

Lixin Zhao,

Wei Yan

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: 15(2), P. 876 - 891

Published: Jan. 5, 2025

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the of and improve psoriasis-like symptoms in both murine cynomolgus monkey models. Mechanistically, directly bound low-density lipoprotein receptor-related protein 1 (LRP1) β-chain abolished its binding transcription factor c-Jun nucleus, which turn inhibited production skin fibroblasts, blocked fibroblast-macrophage crosstalk, ameliorated progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction like inflammation. Taken together, from clinical samples combined various mouse models, revealed pathogenesis perspective provided foundation for as novel potential target treatment.

Language: Английский

Citations

0
Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes DOI Creative Commons
Kai He, Dong Xue, Tian-Jing Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 22, 2025

Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among elderly population. Smoking significantly increases AMD risk, yet mechanisms remain unclear. Here, we investigate role Sema4D-PlexinB1 axis in progression AMD, which highly activated by smoking. Using patient-derived samples mouse models, discover that smoking presence Sema4D on surface CD8+ T cells migrate into choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 interact with its receptor PlexinB1 pericytes. This leads to ROR2-mediated phosphorylation pericyte activation, thereby disrupting vascular homeostasis promoting neovascularization. Inhibition reduces CNV improves benefit anti-VEGF treatment. In conclusion, this study unveils molecular through exacerbates pathology, presents potential therapeutic strategy targeting augment current treatments. shows worsens neovascular age-related pathway. Targeting enhances therapy efficacy, offering approach.

Language: Английский

Citations

0
The Critical Role and Therapeutic Potential of the CXCR Family in Skin Diseases DOI Creative Commons
Jin Xu, Chaoyi Wang, Yundong Xu

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(5)

Published: April 29, 2025

The C-X-C chemokine receptors (CXCR) receptor family, consisting of seven primary members (CXCR1–CXCR7), is crucial in regulating immune cell recruitment, angiogenesis, cellular proliferation, and maintaining skin homeostasis functions. This review evaluates the expression roles CXCR across a range cells, including keratinocytes, fibroblasts, endothelial melanocytes, various cells such as T dendritic macrophages. Aberrations signaling have been associated with variety disorders, psoriasis, atopic dermatitis, acne, cancers. Despite significant advancements field, several critical questions persist. These include differential effects distinct pathologies intricate interactions between their ligands within diverse microenvironments. Moreover, therapeutic targeting family remains unresolved, necessitating further research into its long-term efficacy possible adverse effects. Future investigations should prioritize these issues to develop more effective strategies for managing diseases, ultimately improving patient outcomes.

Language: Английский

Citations

0
Exploring the Common Pathogenic Mechanisms of Psoriasis and Atopic Dermatitis: The Interaction between SGK1 and TIGIT Signaling Pathways DOI

Canbin Dong,

Jui‐Ming Lin, Yilun Wang

et al.

Inflammation, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

0
Multitranscriptome analysis revealed that stromal cells in the papillary dermis promote angiogenesis in psoriasis vulgaris DOI Creative Commons
Bo Zhang, Junpu Mei, Qijun Liao

et al.

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Abstract Background The pathogenesis of psoriasis is incompletely understood. Growing evidence suggests the involvement stromal cells in inflammatory process. Objectives To investigate roles cells, including fibroblasts, vascular endothelial (VECs) and smooth muscle (VSMCs), psoriatic microenvironment, possible underlying mechanisms involved. Methods We used a combination single-cell, spatial transcriptome bulk RNA sequencing lesional nonlesional skin samples from patients with vulgaris (PV) healthy unaffected individuals. Results By analysing transcriptomes 364 098 single we uncovered WNT5A+ (Wnt-5a) ITIH5+ (inter-α-trypsin inhibitor heavy chain 5) VECs VCAN+ (versican) VSMCs, significantly increased proportions these papillary dermis skin. defined eight unique subclusters fibroblasts observed shift WIF1+ (Wnt inhibitory factor 1) toward abnormal activation noncanonical Wnt signalling pathway angiogenic proinflammatory capabilities. VSMCs were able to undergo phenotypic transformation contractile synthetic phenotype during development inflammation. found have an essential role regulating angiogenesis remodelling pathological changes seen PV. Ligand receptor analyses that are extensively implicated interactions various cell types, especially TIH5+ dermis. Conclusions Interactions identified as pathogenic elements Improving microenvironment by targeting might be potential treatment strategy

Language: Английский

Citations

0