Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis
| Autor: | Alan C. Chen, Nancy C. Andrews, Renee Ned-Sykes, Adriana Donovan |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition Genotype Iron Transferrin receptor Biology Endocytosis Mice Intestinal mucosa Receptors Transferrin medicine Animals Homeostasis Intestinal Mucosa Receptor Alleles Cell Proliferation Mice Knockout Recombination Genetic chemistry.chemical_classification Multidisciplinary Gene Expression Profiling Stem Cells Brain Gene Expression Regulation Developmental Biological Sciences Intestinal epithelium Epithelium Cell biology Intestines Phenotype medicine.anatomical_structure chemistry Biochemistry Transferrin Mutation Female Stem cell |
| Zdroj: | Proceedings of the National Academy of Sciences. 112:11714-11719 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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