Open AccessZinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress
Author(s) -
Wakana Ohashi,
Shunsuke Kimura,
Toshihiko Iwanaga,
Yukihiro Furusawa,
Tarou Irié,
Hironori Izumi,
Takashi Watanabe,
Atsushi Hijikata,
Takafumi Hara,
Osamu Ohara,
Haruhiko Koseki,
Toshiro Sato,
Sylvie Robine,
Hisashi Mori,
Yoshiyuki Hattori,
Hiroshi Watarai,
Kenji Mishima,
Hiroshi Ohno,
Koji Hase,
Toshiyuki Fukada
Publication year - 2016
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006349
Subject(s) - biology , microbiology and biotechnology , intestinal epithelium , progenitor cell , stem cell , homeostasis , unfolded protein response , endoplasmic reticulum , intestinal mucosa , paneth cell , regeneration (biology) , crypt , progenitor , immunology , epithelium , small intestine , endocrinology , medicine , genetics
Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells. Zip7 deficiency led to the loss of Olfm4 + intestinal stem cells and the degeneration of post-mitotic Paneth cells, indicating a fundamental requirement for Zip7 in homeostatic intestinal regeneration. Taken together, these findings provide evidence for the importance of ZIP7 in maintenance of intestinal epithelial homeostasis through the regulation of ER function in proliferative progenitor cells and maintenance of intestinal stem cells. Therapeutic targeting of ZIP7 could lead to effective treatment of gastrointestinal disorders.