Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis.

Abstract

Psoriasis is a chronic inflammatory skin disease severely affecting patients' physical and psychological well-being. Aberrant keratin expression in psoriasis plays a crucial role in keratinocyte dysfunction and disease development. Little is yet known about the mechanism of this keratin dysregulation. VEGF (Vascular endothelial growth factor) is significantly elevated in psoriatic patients and VEGFRs are detected on keratinocytes, leading to our hypothesis that this keratin dysregulation may be regulated by VEGF. In this study, we showed that VEGFR2 was overexpressed in psoriatic epidermis and was correlated with K (keratin) 6, K16&K17 upregulation and K1&K10 downregulation. VEGF increased both mRNA and protein levels of K6, K16&K17 and decreased those of K1&K10 in NHEKs (normal human epidermal keratinocytes). Further we identified activation of STAT3, ERK1/2, and p38 pathways in VEGF-treated NHEKs. Using specific pathway antagonists and siRNAs we found that VEGF induced K6, K16&K17 via these three pathways and reduced K1&K10 via ERK1/2. Finally, VEGF-induced aberrant keratin expression pattern and epidermal thickening were confirmed in a VEGF-local-injection mouse model. Collectively, we demonstrated that VEGF was associated with aberrant keratin expression pattern in psoriasis and provided a new insight into the role of VEGF in psoriasis pathogenesis, indicating VEGF as a potential therapeutic target.

• Authors: Man Jiang, Bing Li, Jieyu Zhang, Lei Hu, Erle Dang, Gang Wang
• Journal: Experimental cell research (Exp Cell Res) Vol. 360 Issue 2 Pg. 310-319 (11 15 2017) ISSN: 1090-2422 [Electronic] United States
• PMID: 28928080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• Vascular Endothelial Growth Factor A
• Keratins

Topics

• Adolescent
• Adult
• Animals
• Cells, Cultured
• Child
• Epidermis (drug effects, metabolism, pathology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Humans
• Keratins (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Psoriasis (genetics, pathology)
• Skin (drug effects, metabolism, pathology)
• Vascular Endothelial Growth Factor A (pharmacology)
• Young Adult