LSR targets YAP to modulate intestinal Paneth cell differentiation

• DOI: 10.1016/j.celrep.2023.113118
• Publication Date: 2023-09-12T13:44:11Z
• Authors: Yanan An; Chao Wang; Baozhen Fan; Ziqi Wang; Ying Li; Feng Kong; Chengjun Zhou; Zhang Cao; Mingxia Wang; Hui Sun; Shengtian Zhao; Yongfeng Gong
• Keywords: Paneth cell; Intestinal epithelium; Intestinal mucosa; Homeostasis

Lipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis pathogenesis disease. By using multiple conditional deletion mouse models ex vivo cultured organoids, find elimination stem cells results the disappearance Paneth without affecting differentiation other cell lineages. Mechanistic studies reveal deficiency increases abundance YAP by modulating phosphorylation proteasomal degradation. Using gain- loss-of-function studies, show protects against necrotizing enterocolitis through enhancement small-intestinal epithelium. Thus, this study identifies as an upstream negative regulator activity, essential factor differentiation, potential therapeutic target enterocolitis.