The Role of p38b MAPK in Age-Related Modulation of Intestinal Stem Cell Proliferation and Differentiation in Drosophila

Aging (Albany NY). 2009 May 21;1(7):637-51. doi: 10.18632/aging.100054.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Aging / physiology*
  • Animals
  • Animals, Genetically Modified / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Proliferation*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / enzymology*
  • Enterocytes / cytology
  • Enterocytes / metabolism
  • Enteroendocrine Cells / cytology
  • Enteroendocrine Cells / metabolism
  • Gene Expression / genetics
  • Intestinal Mucosa / metabolism
  • Intestines / cytology*
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinase 11 / genetics
  • Mitogen-Activated Protein Kinase 11 / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oxidative Stress / physiology
  • Paraquat / pharmacology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Su(H) protein, Drosophila
  • Transcription Factors
  • delta protein
  • esg protein, Drosophila
  • pros protein, Drosophila
  • Pvr protein, Drosophila
  • Receptor Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinase 11
  • Paraquat