LIF is essential for ISC function and protects against radiation-induced gastrointestinal syndrome. Academic Article uri icon

Overview

abstract

  • Leukemia inhibitory factor (LIF) is a cytokine essential for maintaining pluripotency of mouse embryonic stem cells. However, its role in adult intestinal stem cells (ISCs) is unclear. The adult intestinal epithelium has a high self-renewal rate driven by ISCs in crypts. Here, we find that LIF is present in the ISC niche in crypts and critical for the function of ISCs in maintaining the intestinal epithelial homeostasis and regeneration. Mechanistically, LIF maintains β-catenin activity through the AKT/GSK3β signaling to regulate ISC functions. LIF deficiency in mice impairs the renewal of the intestinal epithelium under the physiological condition. Further, LIF deficiency in mice impairs the regeneration of intestinal epithelium in response to radiation and shortens the lifespan of mice after high doses of radiation due to gastrointestinal (GI) syndrome, which can be rescued by administering recombinant LIF (rLIF). Importantly, LIF exhibits a radioprotective role in wild-type (WT) mice by protecting mice from lethal radiation-induced GI syndrome; administering rLIF promotes intestinal epithelial regeneration and prolongs survival in WT mice after radiation. These results reveal a previously unidentified and a crucial role of LIF in ensuring ISC function, promoting regeneration of the intestinal epithelium in response to radiation and protecting against radiation-induced GI syndrome.

publication date

  • July 27, 2020

Research

keywords

  • Intestines
  • Leukemia Inhibitory Factor
  • Radiation Injuries
  • Stem Cells

Identity

PubMed Central ID

  • PMC7385639

Scopus Document Identifier

  • 85088585762

Digital Object Identifier (DOI)

  • 10.1016/j.fertnstert.2008.06.047

PubMed ID

  • 32719388

Additional Document Info

volume

  • 11

issue

  • 7