Beta-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells

Autor: Matthew D. Keefe, Jean Paul De La O, Matthew A. Firpo, L. Charles Murtaugh, Ameena Khan, Hui Wang
Rok vydání: 2012
Předmět:
Aging
medicine.medical_specialty
Cellular differentiation
Neuroscience (miscellaneous)
lcsh:Medicine
Medicine (miscellaneous)
Acinar Cells
Biology
General Biochemistry
Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
Immunology and Microbiology (miscellaneous)
Internal medicine
lcsh:Pathology
Acinar cell
medicine
Animals
Homeostasis
Humans
Regeneration
Cell Lineage
Progenitor cell
beta Catenin
Cell Proliferation
030304 developmental biology
Mice
Knockout
Acinar cell proliferation
0303 health sciences
geography
geography.geographical_feature_category
Regeneration (biology)
lcsh:R
Wnt signaling pathway
Cell Differentiation
Islet
Embryonic stem cell
Pancreas
Exocrine
Cell biology
Endocrinology
Animals
Newborn
Pancreatitis
030220 oncology & carcinogenesis
Ceruletide
Gene Deletion
lcsh:RB1-214
Research Article
Zdroj: Disease Models & Mechanisms
Disease Models & Mechanisms, Vol 5, Iss 4, Pp 503-514 (2012)
ISSN: 1754-8411
1754-8403
DOI: 10.1242/dmm.007799
Popis: SummaryThe size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth, and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required for generation of exocrine acinar cells in utero, this gene has been ascribed various functions in the postnatal pancreas including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt/β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt/β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and may therefore contribute to the resolution of acute or chronic pancreatitis.
Databáze: OpenAIRE
Externí odkaz: