All ETDs from UAB

Advisory Committee Chair

Melissa L Harris

Advisory Committee Members

Anita Hjelmeland

Deborah Lang

Trygve O Tollefsbol

Deeann Wallis

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Neuropeptide Y (NPY) is an abundant peptide with pleiotropic roles in a variety of biological processes throughout multiple tissues. Despite its known functions in various tissues, the specific effects of NPY in the skin remain poorly understood. Elevated NPY expression in the skin has been associated with inflammatory skin diseases such as atopic dermatitis, psoriasis, and vitiligo. Additionally, genetic mutations in the NPY gene have been associated with increased susceptibility for vitiligo in some populations. This clinical evidence of NPY’s involvement in skin pathology are merely correlative, and there have yet to be empirical data to determine whether NPY can contribute to skin disease. To begin the long-awaited investigations into the roles of NPY in skin pathology, we utilized the B6;129S4-Npytm2Rpa/J mouse line that overexpresses NPY from its endogenous promoter. With this mouse model of entopic overexpression of NPY, we provide the first evidence of NPY’s contributions to skin pathology. We show that this mouse line exhibits chronic overexpression of Npy in the skin, and that this skin-specific overexpression of NPY induces inflammation, fibrosis, hyperkeratosis, and premature hair graying. Furthermore, the transcriptome of the skin from NPY-overexpressing mice iv is similar to the transcriptomes of human and mouse samples of atopic dermatitis and psoriasis. These collective studies indicate that overexpression of NPY in the skin is sufficient to induce pathology and identify the B6;129S4-Npytm2Rpa/J mouse as a novel and much-anticipated model with which to investigate NPY-mediated inflammatory skin diseases.

NPY-RNAseq_Supplementary-File.xlsx (17384 kB)
Supplementary RNA Sequence Data File

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