ZAG Regulates the Skin Barrier and Immunity in Atopic Dermatitis

Abstract

Adipokines modulate immune responses and lipid metabolism in allergic disease; however, little is known about their role in the skin barrier and atopic dermatitis (AD). We identified ZAG, an adipokine that regulates lipid mobilization, as a biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. ZAG was primarily detected in the stratum corneum along with FLG and LOR. Knockdown of ZAG with short hairpin RNA resulted in decreased FLG and increased TSLP. Topical ZAG treatment in AD mice recovered ZAG expression in the skin and improved AD-like symptoms, transepidermal water loss, and ceramide levels. Furthermore, topical ZAG treatment induced immunoregulatory effects, including reduction of IL-4, IL-17, and IFN-g and increased Foxp3 in the skin and lymphoid organs. Interestingly, ZAG treatment also recovered decreased levels of ADAM17, an important player in skin barrier function and immune response in AD. Thus, ZAG deficiency is closely related to skin barrier function and the immune abnormalities of AD, and we suggest that restoration of ZAG may be a promising therapeutic option for the treatment of AD.

Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

“…Also, we detected a decreased expression of AZGP which is correlated with abnormalities in lipid metabolism. Recently, AZGP has been suggested to be a possible biomarker and therapeutic target in AD 49 . In our study, alteration in lipid metabolism has been highlighted by lower expression of PLB1, PLBD2, PLD3, DHCR7, C11orf54, ACPP, ANXA7 and NPM1.…”

Changes of serum zinc-α2-glycoprotein level and analysis of its related factors in gestational diabetes mellitus:a cross-sectional study

“…ZAG is widely found in human body uids, with carrier protein, ribonuclease activity and other functions 9 . In recent years, many studies have shown that ZAG has function of regulating immunity, cell adhesion, and regulating of melanin production 13,14 . Some studies [15][16][17] also pointed out that ZAG can be used as a biomarker for the early diagnosis of cancer, and its can participate in regulating tumor cell proliferation and glucose metabolism 18 .…”

Barrier defect in atopic dermatitis – possibilities and limits of basic skin therapy

“…The monomers bind keratin filaments and finally form the scaffold of corneocytes. In a recent work, the protein zinc α-2-glycoprotein (ZAG) produced by adipocytes and keratinocytes of the skin was identified as a positive regulator of filaggrin expression [ 15 ]. ZAG, which is also proclaimed as a biomarker for AD, was also able to positively affect the levels at the epidermal cytokine thymic stromal lymphopoietin (TSLP) in this study.…”