Metformin Protects the Intestinal Barrier by Activating Goblet Cell Maturation and Epithelial Proliferation in Radiation-Induced Enteropathy.
Hyosun JangSoyeon KimHyewon KimSu Hyun OhSeo Young KwakHyun-Woo JooSeung-Bum LeeWon Il JangSunhoo ParkSehwan ShimPublished in: International journal of molecular sciences (2022)
Radiotherapy or accidental exposure to high-dose radiation can cause severe damage to healthy organs. The gastrointestinal (GI) tract is a radiation-sensitive organ of the body. The intestinal barrier is the first line of defense in the GI tract, and consists of mucus secreted by goblet cells and a monolayer of epithelium. Intestinal stem cells (ISCs) help in barrier maintenance and intestinal function after injury by regulating efficient regeneration of the epithelium. The Wnt/β-catenin pathway plays a critical role in maintaining the intestinal epithelium and regulates ISC self-renewal. Metformin is the most widely used antidiabetic drug in clinical practice, and its anti-inflammatory, antioxidative, and antiapoptotic effects have also been widely studied. In this study, we investigated whether metformin alleviated radiation-induced enteropathy by focusing on its role in protecting the epithelial barrier. We found that metformin alleviated radiation-induced enteropathy, with increased villi length and crypt numbers, and restored the intestinal barrier function in the irradiated intestine. In a radiation-induced enteropathy mouse model, metformin treatment increased tight-junction expression in the epithelium and inhibited bacterial translocation to mesenteric lymph nodes. Metformin increased the number of ISCs from radiation toxicity and enhanced epithelial repair by activating Wnt/β-catenin signaling. These data suggested that metformin may be a potential therapeutic agent for radiation-induced enteropathy.
Keyphrases
- radiation induced
- stem cells
- radiation therapy
- high dose
- mouse model
- signaling pathway
- anti inflammatory
- lymph node
- clinical practice
- poor prognosis
- cell proliferation
- induced apoptosis
- emergency department
- low dose
- squamous cell carcinoma
- early stage
- blood brain barrier
- cell cycle arrest
- early onset
- electronic health record
- mass spectrometry
- cell death
- mesenchymal stem cells
- big data
- bone marrow
- smoking cessation
- data analysis
- adverse drug
- sentinel lymph node