Earticle

초록

영어

Background: In the aftermath of September 11 attacks, the radiobiology community sought novel radiation mitigators capable of preventing death when administered 24 hours or later after exposure to lethal ionizing radiation. The survival and expansion of normal stem cells are crucial for restoring tissue integrity in time to prevent mortality. While U.S. Food and Drug Administration- approved drugs for acute radiation syndrome primarily target the hematopoietic system, restoring the integrity of the intestinal lining is equally important for survival. However, the radiation response of the intestinal stem cell (ISC) population and its niche environment is not as well understood as that of the bone marrow. The aim of this study is to explore early transcriptomic changes in the small intestine after a lethal dose of total body irradiation (TBI) and during subsequent recovery. Materials and Methods: C3H/Sed/Kam mice were irradiated with a TBI dose of 16 Gy, the published 70% lethal dose within 10 days. The compound 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) was administered 24 hours post-irradiation. RNAs from the proximal duodenum were extracted at 28, 72, and 96 hours post-irradiation and subjected to RNA-sequencing. Differentially expressed genes were analyzed using gene-set enrichment analysis. Results and Discussion: Radiation induced significant transcriptomic changes known to precede the death of lymphatic endothelial and epithelial cells. Upregulation of Lgr5+ ISC gene signature was observed during recovery. NSPP treatment further amplified the activation of ISCassociated genes and other regenerative markers. Notably, gene Psrc1 showed strong activation throughout the recovery process, highlighting its potential role in this regenerative response. Conclusion: Our findings highlight potential additional intervention points for mitigating radiation- induced damage in the intestines beyond solely targeting programmed cell death. These insights may contribute to the development of more effective radioprotective approaches, ultimately improving clinical outcomes for individuals undergoing radiotherapy or exposed to highdose radiation.

목차

ABSTRACT
Introduction
Materials and Methods
1. Animals
2. Irradiation
3. In Vivo Drug Administration
4. RNA Isolation
5. Bulk RNA Sequencing
6. Hematoxylin and Eosin Staining
7. TdT-Mediated dUTP Nick-End Labeling Staining
8. Statistics
Results
1. Radiation-Induced Apoptosis in Murine Small Intestine and Its Mitigation by NSPP
2. Total Body Irradiation Induces Distinct Gene Expression Profiles in Murine Small Intestines
3. Upregulation of the Lgr5+ Intestinal Stem Cell Gene Signature during Recovery
4. Early Transcriptomic Changes in the Small Intestines Following NSPP Mitigation
5. Transcriptomic Changes during Recovery Following NSPP Mitigation
6. Lgr5+ Intestinal Stem Cell Gene Signature Changes during Recovery Following NSPP Mitigation
Discussion
Conclusion
Article Information
References

키워드

저자

• Ling He [ Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA ] Corresponding Author
• Kruttika Bhat [ Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA ]
• Frank Pajonk [ Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  방사선방어학회지 [Journal of Radiation Protection and Research]

• 간기

  계간

• pISSN

  2508-1888

• 수록기간

  1976~2026

• 등재여부

  KCI 등재,SCOPUS

• 십진분류

  KDC 559 DDC 629