Significance of vascular endothelial growth factor and CD31 and morphometric analysis of microvessel density by CD31 receptor expression as an adjuvant tool in diagnosis of psoriatic lesions of skin

Chawla, Nitika; Kataria, Sant Prakash; Aggarwal, Kamal; Chauhan, Pardeep; Kumar, Dinesh

doi:10.4103/ijpm.ijpm_862_15

Cited by 10 publications

(7 citation statements)

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“…Fisetin treatment increased the number of effectors associated with the MAPK signaling pathway, the TNF signaling pathway, the small GTPase mediated signal transduction pathway, the inositol phosphate metabolism pathway, autophagy, and the VEGF signaling system, which are all known to be dysregulated or involved in psoriasis ( Figure 1B ). Overlapping DEGs when the three groups (activated vs Control, activated + fisetin vs activated, and activated + Rapamycin vs activated) were analyzed by Metascape ( Figures 1C, D ) ( 36 ).…”

Section: Resultsmentioning

confidence: 99%

“…The presence of endothelial cells in a tissue, identified using the marker cluster of differentiation 31 (CD31), largely enhances angiogenesis. A vertically arranged cluster of CD31-positive cells in the dermis and altered epidermal appearance are both favorable indicators of psoriasis ( 36 , 49 , 50 ). We examined the effect of fisetin treatment on the psoriatic skin vasculature (angiogenesis).…”

Section: Resultsmentioning

confidence: 99%

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Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

et al. 2023

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

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

et al. 2023

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“…showed that overexpression of VEGF correlated well with increased MVD which indicated an increasing trend in psoriasis when compared with the psoriasiform lesions. [ 18 ]…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor and microvessel density in psoriatic skin lesions

Rajan

Suresh

Rajashekar

2018

Indian Dermatol Online J

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“…To characterize the histopathological differences between these mouse strains in greater detail, we determined the numbers of endothelial (CD31 + ) cells, macrophages/ dendritic (F4/80 + ) cells (macrophages/DCs), and T (CD3 + ) cells in representative skin sections (Figure 4B). All three cell populations have been identified as important drivers of AIPD and psoriasis, with increased numbers detected in psoriasiform and psoriatic skin [9,15,21,22]. While the numbers of dermal CD3 + T cells and F4/80 + macrophages/DCs were significantly lower in skin specimens from Itga11 À/À mice at the final time point (day 4), we detected no differences in the Itga11 is a modulator of psoriasiform dermatitis 187 number of CD31 + endothelial cells (Figure 4B).…”

Section: Itga11 à/à Mice Are Partially Protected From Developing Aipdmentioning

confidence: 99%

Forward genetics and functional analysis highlight Itga11 as a modulator of murine psoriasiform dermatitis

Bieber

Bezdek

Gupta

et al. 2023

The Journal of Pathology

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Psoriasis is a chronic inflammatory skin condition. Repeated epicutaneous application of Aldara® (imiquimod) cream results in psoriasiform dermatitis in mice. The Aldara®‐induced psoriasiform dermatitis (AIPD) mouse model has been used to examine the pathogenesis of psoriasis. Here, we used a forward genetics approach in which we compared AIPD that developed in 13 different inbred mouse strains to identify genes and pathways that modulated disease severity. Among our primary results, we found that the severity of AIPD differed substantially between different strains of inbred mice and that these variations were associated with polymorphisms in Itga11. The Itga11 gene encodes the integrin α11 subunit that heterodimerizes with the integrin β1 subunit to form integrin α11β1. Less information is available about the function of ITGA11 in skin inflammation; however, a role in the regulation of cutaneous wound healing, specifically the development of dermal fibrosis, has been described. Experiments performed with Itga11 gene‐deleted (Itga11−/−) mice revealed that the integrin α11 subunit contributes substantially to the clinical phenotype as well as the histopathological and molecular findings associated with skin inflammation characteristic of AIPD. Although the skin transcriptomes of Itga11−/− and WT mice do not differ from one another under physiological conditions, distinct transcriptomes emerge in these strains in response to the induction of AIPD. Most of the differentially expressed genes contributed to extracellular matrix organization, immune system, and metabolism of lipids pathways. Consistent with these findings, we detected a reduced number of fibroblasts and inflammatory cells, including macrophages, T cells, and tissue‐resident memory T cells in skin samples from Itga11−/− mice in response to AIPD induction. Collectively, our results reveal that Itga11 plays a critical role in promoting skin inflammation in AIPD and thus might be targeted for the development of novel therapeutics for psoriasiform skin conditions. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Significance of vascular endothelial growth factor and CD31 and morphometric analysis of microvessel density by CD31 receptor expression as an adjuvant tool in diagnosis of psoriatic lesions of skin

Cited by 10 publications

References 0 publications

Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

Expression of vascular endothelial growth factor and microvessel density in psoriatic skin lesions

Forward genetics and functional analysis highlight Itga11 as a modulator of murine psoriasiform dermatitis

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