Abstract
It is important to understand how age-related changes in intestinal stem cells (ISCs) may contribute to age-associated intestinal diseases, including cancer. Drosophila midgut is an excellent model system for the study of ISC proliferation and differentiation. Recently, age-related changes in the Drosophila midgut have been shown to include an increase in ISC proliferation and accumulation of mis-differentiated ISC daughter cells. Here, we show that the p38b MAPK pathway contributes to the age-related changes in ISC and progenitor cells in Drosophila. D-p38b MAPK is required for an age-related increase of ISC proliferation. In addition, this pathway is involved in age and oxidative stress-associated mis-differentiation of enterocytes and upregulation of Delta, a Notch receptor ligand. Furthermore, we also show that D-p38b acts downstream of PVF2/PVR signaling in these age-related changes. Taken together, our findings suggest that p38 MAPK plays a crucial role in the balance between ISC proliferation and proper differentiation in the adult Drosophila midgut.
Keywords:
Delta/Notch pathway; Drosophila; PVR signaling; differentiation; gut; intestinal stem cell; oxidative stress; p38b MAPK; aging; proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult Stem Cells / cytology*
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Adult Stem Cells / metabolism
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Aging / physiology*
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Animals
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Animals, Genetically Modified / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Proliferation*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila melanogaster / cytology*
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Drosophila melanogaster / enzymology*
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Enterocytes / cytology
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Enterocytes / metabolism
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Enteroendocrine Cells / cytology
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Enteroendocrine Cells / metabolism
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Gene Expression / genetics
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Intestinal Mucosa / metabolism
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Intestines / cytology*
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mitogen-Activated Protein Kinase 11 / genetics
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Mitogen-Activated Protein Kinase 11 / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oxidative Stress / physiology
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Paraquat / pharmacology
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Repressor Proteins
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Su(H) protein, Drosophila
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Transcription Factors
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delta protein
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esg protein, Drosophila
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pros protein, Drosophila
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Pvr protein, Drosophila
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Receptor Protein-Tyrosine Kinases
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Mitogen-Activated Protein Kinase 11
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Paraquat