Blocking VEGFA Interaction May Prevent Psoriasis Development

Study Overview

A recent study published in Science Advances reveals that inhibiting the interaction between Flt1 and Nrp1 with vascular endothelial growth factor A (VEGFA) in the skin epidermis can prevent the onset of psoriasis. This skin inflammatory disorder affects approximately three percent of the global population, leading to the formation of raised, red, scaly patches on various body areas, particularly the elbows, knees, and scalp.

Psoriasis and Its Implications

Psoriasis is associated with an increased risk of developing arthritis, metabolic syndrome, and bowel inflammatory diseases. The condition is marked by the hyperproliferation of keratinocytes, the epidermal cells responsible for producing keratin. This hyperproliferation disrupts epidermal differentiation, intensifies inflammation, and stimulates blood vessel production. Previous studies have highlighted the significance of the interaction between keratinocytes, blood vessels, and immune cells in psoriasis development, although the specific roles of these cells remain largely undefined.

VEGFA’s Role in Psoriasis

Individuals with psoriasis exhibit an overexpression of VEGFA, leading to an increased formation of blood vessels. Research has shown a correlation between the severity of the disease and VEGFA levels, with experimental evidence indicating that blocking VEGFA can alleviate skin symptoms in mouse models of psoriasis-like conditions. However, the exact molecular mechanisms of VEGFA signaling and its effects on different cell populations in the skin are still being explored.

Research Findings

In this study, researchers utilized genetically engineered mouse models of psoriasis to investigate the contributions of epidermal Flt1 and Nrp1 to psoriasis development and treatment. They measured epidermal thickness in psoriasis lesions, cell proliferation, immune cell infiltration, and microvascular density related to VEGFA overexpression. The findings revealed that deleting epidermal Nrp1 or Flt1 completely inhibited psoriasis development induced by VEGFA overexpression. This deletion effectively reduced epidermal thickness, cell proliferation, and dermal immune infiltrate.

Potential New Treatment Approaches

The study suggests a promising new treatment for psoriasis through the administration of Nrp1-blocking antibodies, which disrupt the interaction between VEGFA and Nrp1. Following treatment with these antibodies, researchers observed normalization of epidermal thickness, cell proliferation, and immune infiltration. Cédric Blanpain, the senior author of the study, noted that targeting the VEGFA/Nrp1 interaction may offer a safer treatment alternative with fewer severe side effects.

Conclusion

These results not only enhance the understanding of the molecular mechanisms underlying psoriasis but also propose two innovative treatment pathways for reversing psoriatic lesions induced by VEGFA. Additionally, the study highlights the autonomous roles of epidermal Flt1 and Nrp1 in mediating psoriasis.

References

1) Benhadou, F., Glitzner, E., Brisebarre, A., Swedlund, B., Song, Y., Dubois, C., … Blanpain, C. (2020, January 1). Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease. Retrieved from https://advances.sciencemag.org/content/6/2/eaax5849/tab-pdf.
2) Psoriasis: Towards a novel therapeutic approach. (2020). Retrieved 11 January 2020, from https://www.eurekalert.org/pub_releases/2020-01/uldb-pta010920.php
Image by PublicDomainPictures from Pixabay