Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis.
Published
Journal Article
Transferrin receptor 1 (Tfr1) facilitates cellular iron uptake through receptor-mediated endocytosis of iron-loaded transferrin. It is expressed in the intestinal epithelium but not involved in dietary iron absorption. To investigate its role, we inactivated the Tfr1 gene selectively in murine intestinal epithelial cells. The mutant mice had severe disruption of the epithelial barrier and early death. There was impaired proliferation of intestinal epithelial cell progenitors, aberrant lipid handling, increased mRNA expression of stem cell markers, and striking induction of many genes associated with epithelial-to-mesenchymal transition. Administration of parenteral iron did not improve the phenotype. Surprisingly, however, enforced expression of a mutant allele of Tfr1 that is unable to serve as a receptor for iron-loaded transferrin appeared to fully rescue most animals. Our results implicate Tfr1 in homeostatic maintenance of the intestinal epithelium, acting through a role that is independent of its iron-uptake function.
Full Text
Duke Authors
Cited Authors
- Chen, AC; Donovan, A; Ned-Sykes, R; Andrews, NC
Published Date
- September 15, 2015
Published In
Volume / Issue
- 112 / 37
Start / End Page
- 11714 - 11719
PubMed ID
- 26324903
Pubmed Central ID
- 26324903
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1511701112
Language
- eng
Conference Location
- United States