2. Academic Validation
  3. LIF is essential for ISC function and protects against radiation-induced gastrointestinal syndrome

LIF is essential for ISC function and protects against radiation-induced gastrointestinal syndrome

  • Cell Death Dis. 2020 Jul 27;11(7):588. doi: 10.1038/s41419-020-02790-6.
Huaying Wang  # 1,  Jianming Wang  # 1,  Yuhan Zhao 1,  Xiao Zhang 2,  Juan Liu 1,  Cen Zhang 1,  Bruce Haffty 1,  Michael Verzi 3,  Lanjing Zhang 1 2 4,  Nan Gao 2,  Zhaohui Feng 5,  Wenwei Hu 6
Affiliations

Affiliations

  • 1 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, 08903, NJ, USA.
  • 2 Department of Biological Sciences, Rutgers University, Newark, 07102, NJ, USA.
  • 3 Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, 08854, NJ, USA.
  • 4 Department of Pathology, Penn Medicine Princeton Medical Center, Plainsboro, 08536, NJ, USA.
  • 5 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, 08903, NJ, USA. [email protected].
  • 6 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, 08903, NJ, USA. [email protected].
  • # Contributed equally.
PMID: 32719388 DOI: 10.1038/s41419-020-02790-6
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.

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