ANGPTL4 Regulates Psoriasis via Modulating Hyperproliferation and Inflammation of Keratinocytes

Abstract

Background: Psoriasis is characterized by keratinocyte proliferation and massive inflammatory leukocytes infiltration, affecting 0.14%–1.99% of the world’s population. Our aim was to identify novel potential therapeutic strategies for psoriasis.Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules that were closely related to psoriasis based on the GSE30999 dataset, which contained expression data from 85 patients with moderate-to-severe psoriasis. Then, angiopoietin-like 4 (ANGPTL4), one of the most related hub genes, was selected for in vitro and in vivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasiform dermatitis in mice and human keratinocytes (HaCaT) cells were used to study the potential roles and mechanisms of ANGPTL4 in psoriasis.Results: WGCNA analysis revealed the turquoise module was most correlated with psoriasis, and ANGPTL4 is one of the most related hub genes that significantly upregulated in psoriasis lesions compared with non-lesional skin. Consistent with the bioinformatic analysis, the expression of ANGPTL4 was significantly upregulated in IMQ-induced psoriasiform skin of mice. Exogenous recombinant ANGPLT4 protein treatment could promote the proliferation and induce the expression of inflammatory cytokines in HaCaTs, whereas silencing of ANGPTL4 effectively inhibited these effects. Then we demonstrated that recombinant ANGPTL4 protein exacerbated psoriasiform inflammation and epidermal hyperproliferation in vivo. Mechanismly, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) pathways were involved in ANGPTL4-mediated regulation of proliferation and inflammation.Conclusion: We found ANGPTL4 was significantly increased in IMQ-induced psoriasiform skin of mice. ANGPTL4 could promote keratinocyte proliferation and inflammatory response via ERK1/2 and STAT3 dependent signaling pathways in psoriasis.

Effect of Deletion of ANGPTL4 Gene on Viability, Migration and Invasion Ability and Apoptosis of Hepatocellular Carcinoma Cells

“…ANGPTL 4 expression was significantly associated with HCC. Previous studies demonstrated overexpression of ANGPTL4 in HCC patients [18].…”

Dissolvable hyaluronic acid microneedles loaded with β-Elemene for the treatment of psoriasis

“…In addition, the exaggerated inflammation in keratinocytes is another key reason for psoriasis (Ni and Lai, 2020). Studies have demonstrated that suppression of keratinocyte inflammation significantly alleviates psoriasis (Zuo et al, 2022). Previous studies have reported that ELE down-regulates the expression of TNF-α and IL-6 in 7,12-dimethylbenz(a)anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mouse skin, indicating the potential antiinflammatory activity of ELE (Hu et al, 2020).…”

Comprehensive Analysis to Identify Rh Family C Glycoprotein (RHCG) as the Causative Gene for Psoriasis and Search for Alternative Treatment Modalities

“…Published microarray data for patients with psoriasis, including GSE13355, 10 GSE30999, 11 and GSE14905, 12 were obtained from the Gene Expression Omnibus (GEO) portal. The GSE13355, GSE30999, and GSE14905 samples were generated using the Affymetrix Human Genome U113 Plus 2.0 Array and included 176 skin samples with psoriasis, and 256 with normal skin.…”