Emerging role of zinc homeostasis by zinc transporter ZIP7 in intestinal homeostatic self-renewal

There has been a growing interest in the biological significance of zinc and its regulatory mechanism in the development of tissue and in the maintenance of tissue homeostasis. The intestinal epithelium undergoes a continuous self-renewing process to maintain the intestinal homeostasis. Moreover, dysregulation of this process often causes various intestinal disorders including inflammatory bowel disease, ulcer, and cancer. However, the molecular basis of zinc-dependent regulation of intestinal epithelial cell turnover is not fully understood. In this research highlight, we describe that the zinc transporter ZIP7 (highly expressed in undifferentiated epithelial cells) plays a critical role in the intestinal epithelial self-renewal process by alleviating the ER stress during vigorous proliferative response. Our findings also provide evidence showing that the fine-tuning of intracellular zinc homeostasis by ZIP7 is essential to maintain epithelial homeostasis in the intestine.