Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

• Published in: International journal of molecular sciences 2021-01, Vol.22 (2), p.931
• Main Authors: Lee, Jihyun, Jung, Yujin, Jeong, Seo Won, Jeong, Ga Hee, Moon, Gue Tae, Kim, Miri
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - antagonists & inhibitors; Adaptor Proteins, Signal Transducing - genetics; Angiogenesis; Angiogenesis inhibitors; Animals; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Diabetic retinopathy; Disease; Disease Models, Animal; Erythema; Extracellular matrix; Gene Expression Regulation - drug effects; Growth factors; Homeostasis; Humans; Immunoreactivity; In vivo methods and tests; Inflammation; Inhibitors; Kinases; Mice; Pathogenesis; Patients; Peptides; Protein-Serine-Threonine Kinases - genetics; Rosacea; Rosacea - drug therapy; Rosacea - genetics; Rosacea - pathology; Signal transduction; Signal Transduction - drug effects; Skin - drug effects; Skin - pathology; Skin diseases; Skin lesions; Stains & staining; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Transcription; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Yes-associated protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22020931

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.