Angiotensin II Type 2 Receptor Is Critical for the Development of Human Fetal Pancreatic Progenitor Cells into Islet-Like Cell Clusters and Their Potential for Transplantation
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AbstractLocal renin-angiotensin systems (RASs) regulate the differentiation of tissue progenitors. However, it is not known whether such systems can regulate the development of pancreatic progenitor cells (PPCs). To address this issue, we characterized the expression profile of major RAS components in human fetal PPC preparations and examined their effects on the differentiation of PPCs into functional islet-like cell clusters (ICCs). We found that expression of RAS components was highly regulated throughout PPC differentiation and that locally generated angiotensin II (Ang II) maintained PPC growth and differentiation via Ang II type 1 and type 2 (AT(1) and AT(2)) receptors. In addition, we observed colocalization of AT(2) receptors with critical beta-cell phenotype markers in PPCs/ICCs, as well as AT(2) receptor upregulation during differentiation, suggesting that these receptors may regulate beta-cell development. In fact, we found that AT(2), but not AT(1), receptor was a key mediator of Ang II-induced upregulation of transcription factors important in beta-cell development. Furthermore, lentivirus-mediated knockdown of AT(2) receptor suppressed the expression of these transcription factors in ICCs. Transplantation of AT(2) receptor-depleted ICCs into immune-privileged diabetic mice failed to ameliorate hyperglycemia, implying that AT(2) receptors are indispensable during ICC maturation in vivo. These data strongly indicate that a local RAS is involved in governing the functional maturation of pancreatic progenitors toward the endocrine lineage. STEM CELLS 2012;30:525-536
All Author(s) ListLeung KK, Liang J, Ma MT, Leung PS
Journal nameSTEM CELLS
Detailed descriptionTo ORKTS: doi: 10.1002/stem.1008
Year2012
Month3
Day1
Volume Number30
Issue Number3
PublisherWILEY-BLACKWELL
Pages525 - 536
ISSN1066-5099
eISSN1549-4918
LanguagesEnglish-United Kingdom
KeywordsDiabetes; Insulin; Islet transplantation; Pancreatic progenitors; Renin-angiotensin system
Web of Science Subject CategoriesBiotechnology & Applied Microbiology; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; Cell & Tissue Engineering; CELL & TISSUE ENGINEERING; Cell Biology; CELL BIOLOGY; Hematology; HEMATOLOGY; Oncology; ONCOLOGY

Last updated on 2020-21-11 at 00:47