Premium
Deletion of claudin‐7 disrupts epithelial cell differentiation in mouse intestines
Author(s) -
Xing Tiaosi,
Ding Lei,
Camacho Rolando,
Chen Yanhua
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1091.1
Subject(s) - claudin , microbiology and biotechnology , tight junction , biology , crypt , enteroendocrine cell , barrier function , goblet cell , intestinal mucosa , paneth cell , microarray analysis techniques , cellular differentiation , progenitor cell , intestinal epithelium , homeostasis , stem cell , epithelium , gene expression , small intestine , medicine , gene , endocrinology , endocrine system , genetics , hormone
The integrity of intestinal mucosa is vital for nutrition absorption and defense against pathogens. Disruption of intestinal epithelial homeostasis leads to a variety of intestinal disorders, such as chronic inflammation, mucosal ulceration, and cancer. Tight junctions are the physical barrier protecting the body from invasion of intestinal lumen pathogens. As one of the tight junction integral membrane proteins, Claudin‐7 plays an essential role in maintaining intestinal structure and mucosal architecture. To dissect the function of claudin‐7 in intestinal epithelial homeostasis, we used the global (gCldn7−/−) and intestinal‐specific (cCldn7−/−) claudin‐7 knockout mice generated recently as our model systems. Through genome‐wide gene‐expression microarray analysis, immunofluoresent light microscopy, immunohistochemistry, as well as Western blotting analysis, we found that epithelial cell differentiation was greatly altered in claudin‐7‐deficient intestines. For example, enterocytes were dramatically reduced in postnatal day 4 gCldn7−/− and 2–4 months old cCldn7−/− mouse intestines. Goblet cells, Paneth cells, enteroendocrine cells and tuft cells were all significantly decreased in cCldn7−/− mouse small intestines. More importantly, the epithelial cell proliferation in claudin‐7‐deficient intestines was no longer limited to the crypt region and low part of villi where epithelial stem cells and fate‐committed progenitor cells are located. We identified a list of gene expression changes related to cell proliferation and differentiation by microarray analysis between the wild type and claudin‐7‐deficient intestines. These findings suggest that claudin‐7 may have a novel, unidentified function regulating epithelial cell renewal in intestines and play a critical role in maintaining the balance of intestinal epithelial cell proliferation and differentiation. Support or Funding Information This study is supported by National Institute of Health grant DK103166.