Cargando…
Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD
BACKGROUND: To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into β-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenit...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Diabetes Association
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663680/ https://www.ncbi.nlm.nih.gov/pubmed/29086539 http://dx.doi.org/10.4093/dmj.2017.41.5.405 |
_version_ | 1783274855402045440 |
---|---|
author | Lee, So-Hyun Rhee, Marie Kim, Ji-Won Yoon, Kun-Ho |
author_facet | Lee, So-Hyun Rhee, Marie Kim, Ji-Won Yoon, Kun-Ho |
author_sort | Lee, So-Hyun |
collection | PubMed |
description | BACKGROUND: To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into β-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenitor cells. Here, we generated insulin-producing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: PMB (pancreatic and duodenal homeobox 1 [Pdx1], V-maf musculoaponeurotic fibrosarcoma oncogene homolog A [MafA], and BETA2/NeuroD). METHODS: By direct injection into the intestine through the cranial mesenteric artery, adenoviruses (Ad) were successfully delivered to the entire intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately infected with the Ad-Pdx1 and triple Ad-PMB. RESULTS: Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 and Ad-PMB compared to control Ad-green fluorescent protein. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine. CONCLUSION: These data indicated that PMB facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. In conclusion, the small intestine is an accessible and abundant source of surrogate insulin-producing cells. |
format | Online Article Text |
id | pubmed-5663680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Korean Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-56636802017-11-01 Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD Lee, So-Hyun Rhee, Marie Kim, Ji-Won Yoon, Kun-Ho Diabetes Metab J Original Article BACKGROUND: To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into β-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenitor cells. Here, we generated insulin-producing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: PMB (pancreatic and duodenal homeobox 1 [Pdx1], V-maf musculoaponeurotic fibrosarcoma oncogene homolog A [MafA], and BETA2/NeuroD). METHODS: By direct injection into the intestine through the cranial mesenteric artery, adenoviruses (Ad) were successfully delivered to the entire intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately infected with the Ad-Pdx1 and triple Ad-PMB. RESULTS: Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 and Ad-PMB compared to control Ad-green fluorescent protein. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine. CONCLUSION: These data indicated that PMB facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. In conclusion, the small intestine is an accessible and abundant source of surrogate insulin-producing cells. Korean Diabetes Association 2017-10 2017-09-05 /pmc/articles/PMC5663680/ /pubmed/29086539 http://dx.doi.org/10.4093/dmj.2017.41.5.405 Text en Copyright © 2017 Korean Diabetes Association http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lee, So-Hyun Rhee, Marie Kim, Ji-Won Yoon, Kun-Ho Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title | Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title_full | Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title_fullStr | Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title_full_unstemmed | Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title_short | Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD |
title_sort | generation of insulin-expressing cells in mouse small intestine by pdx1, mafa, and beta2/neurod |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663680/ https://www.ncbi.nlm.nih.gov/pubmed/29086539 http://dx.doi.org/10.4093/dmj.2017.41.5.405 |
work_keys_str_mv | AT leesohyun generationofinsulinexpressingcellsinmousesmallintestinebypdx1mafaandbeta2neurod AT rheemarie generationofinsulinexpressingcellsinmousesmallintestinebypdx1mafaandbeta2neurod AT kimjiwon generationofinsulinexpressingcellsinmousesmallintestinebypdx1mafaandbeta2neurod AT yoonkunho generationofinsulinexpressingcellsinmousesmallintestinebypdx1mafaandbeta2neurod |