Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
1,2-propanediol ameliorated radiation-induced intestinal injury in mice
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 11 March 2026

1,2-propanediol ameliorated radiation-induced intestinal injury in mice

  • Jiwei Zhao2 na1 nAff1,
  • Chunan Zhao na1 nAff1,
  • Xing Shen na1 nAff1,
  • Ying Jiang1,
  • Xun Wang1,
  • Aoqiang Ji1,
  • Xuewen Zhang1,
  • Shuang Xing1,
  • Gang Sun2,
  • He Xiao1 &
  • …
  • Zuyin Yu1 

Scientific Reports , Article number:  (2026) Cite this article

  • 1114 Accesses

  • 15 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer
  • Drug discovery
  • Gastroenterology

Abstract

Radiotherapy is constricted by collateral normal tissue injury during treatment, particularly the gastrointestinal tracts, which is usually referred as radiation-induced gastrointestinal syndrome (RIGS). Currently, there is no FDA-approved agent for the prevention or treatment of RIGS. By using a mice model of RIGS, we demonstrated that 1,2-propanediol (1,2-PD) prevents radiation-induced fatal intestinal injury and significantly increases mice survival following lethal doses of radiation. 1,2-PD pretreatment also enhanced the survival of Lgr5+ISCs and improved crypts regeneration after radiation. Moreover, we confirmed 1,2-PD induces dormant cell cycle arrest in enterocytes and ameliorates DNA damage both in vitro and in vivo. Although we did have observed 1,2-PD pretreatment inhibiting P53-PUMA signal pathway, but fail to prove its relation with radiation resistance. In RNA sequencing, we have observed 1,2-PD pretreatment significantly upregulates the Hif-2α, Hif-3α and PPARα target gene ACOX2, whilst downregulating the cell cycle drivers E2f3 and Cyclin D2. These results demonstrate that ISCs play a key role in radiation-induced intestinal regeneration and that 1,2-PD acts as a potent intestinal radioprotector

Similar content being viewed by others

p53 promotes revival stem cells in the regenerating intestine after severe radiation injury

Article Open access 08 April 2024

p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome

Article Open access 02 January 2024

Single-cell map of dynamic cellular microenvironment of radiation-induced intestinal injury

Article Open access 09 December 2023

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The raw RNA-seq data reported in this study have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject accession number PRJNA1358381.

References

  1. Hauer-Jensen, M., Denham, J. W. & Andreyev, H. J. Radiation enteropathy–pathogenesis, treatment and prevention. Nat. Rev. Gastroenterol. Hepatol. 11, 470–479 (2014).

    Google Scholar 

  2. Kirsch, D. G. et al. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 327, 593–596 (2010).

    Google Scholar 

  3. Takeda, N. et al. Interconversion between intestinal stem cell populations in distinct niches. Science 334, 1420–1424 (2011).

    Google Scholar 

  4. Li, L. & Clevers, H. Coexistence of quiescent and active adult stem cells in mammals. Science 327, 542–545 (2010).

    Google Scholar 

  5. Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).

    Google Scholar 

  6. Schuijers, J., van der Flier, L. G., van Es, J. & Clevers, H. Robust cre-mediated recombination in small intestinal stem cells utilizing the olfm4 locus. Stem Cell Reports 3, 234–241 (2014).

    Google Scholar 

  7. Sangiorgi, E. & Capecchi, M. R. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40, 915–920 (2008).

    Google Scholar 

  8. Munoz, J. et al. The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent “+4” cell markers. EMBO J. 31, 3079–3091 (2012).

    Google Scholar 

  9. Barker, N., van Oudenaarden, A. & Clevers, H. Identifying the stem cell of the intestinal crypt: Strategies and pitfalls. Cell Stem Cell 11, 452–460 (2012).

    Google Scholar 

  10. Tian, H. et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255–259 (2011).

    Google Scholar 

  11. Metcalfe, C., Kljavin, N. M., Ybarra, R. & de Sauvage, F. J. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14, 149–159 (2014).

    Google Scholar 

  12. Leibowitz, B. J. et al. Uncoupling p53 functions in radiation-induced intestinal damage via PUMA and p21. Mol. Cancer Res. 9, 616–625 (2011).

    Google Scholar 

  13. Sullivan, J. M. et al. p21 protects “Super p53” mice from the radiation-induced gastrointestinal syndrome. Radiat. Res. 177, 307–310 (2012).

    Google Scholar 

  14. Qiu, W. et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell 2, 576–583 (2008).

    Google Scholar 

  15. Ruddick, J. A. Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol. Appl. Pharmacol. 21, 102–111 (1972).

    Google Scholar 

  16. Yi, L. et al. The protective effects of 1,2-propanediol against radiation-induced hematopoietic injury in mice. Biomed. Pharmacother. 114, 108806 (2019).

    Google Scholar 

  17. Whaley, D. et al. Cryopreservation: An overview of principles and cell-specific considerations. Cell Transplant. 30, 963689721999617 (2021).

    Google Scholar 

  18. Weeden, C. E. & Asselin-Labat, M. L. Mechanisms of DNA damage repair in adult stem cells and implications for cancer formation. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 89–101 (2018).

    Google Scholar 

  19. Wei, L. et al. Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice. J. Clin. Invest. 126, 4076–4087 (2016).

    Google Scholar 

  20. Yuan, Q. et al. Disulfiram protects against radiation-induced intestinal injury in mice. Front. Pharmacol. 13, 852669 (2022).

    Google Scholar 

  21. Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. & Bonner, W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858–5868 (1998).

    Google Scholar 

  22. Prabhu, K. S. et al. H2AX: A key player in DNA damage response and a promising target for cancer therapy. Biomed. Pharmacother. 175, 116663 (2024).

    Google Scholar 

  23. Chang, P. Y., Qu, Y. Q., Wang, J. & Dong, L. H. The potential of mesenchymal stem cells in the management of radiation enteropathy. Cell Death Dis. 6, e1840 (2015).

    Google Scholar 

  24. Achison, M. & Hupp, T. R. Hypoxia attenuates the p53 response to cellular damage. Oncogene 22, 3431–3440 (2003).

    Google Scholar 

  25. Li, L. et al. Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation. Cell Death Discov. 10, 164 (2024).

    Google Scholar 

  26. Leone, G. et al. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev. 12, 2120–2130 (1998).

    Google Scholar 

  27. Nan, Y. M., Wang, R. Q. & Fu, N. Peroxisome proliferator-activated receptor α, a potential therapeutic target for alcoholic liver disease. World J. Gastroenterol. 20, 8055–8060 (2014).

    Google Scholar 

  28. Yue, R. et al. Activation of PPARα-catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance. Free Radic. Biol. Med. 174, 249–263 (2021).

    Google Scholar 

  29. Sherr, C. J. D-type cyclins. Trends Biochem. Sci. 20, 187–190 (1995).

    Google Scholar 

  30. Yan, K. S. et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl. Acad. Sci. U. S. A. 109, 466–471 (2012).

    Google Scholar 

  31. Koo, B. K. & Clevers, H. Stem cells marked by the R-spondin receptor LGR5. Gastroenterology 147, 289–302 (2014).

    Google Scholar 

  32. Zhu, Y., Huang, Y. F., Kek, C. & Bulavin, D. V. Apoptosis differently affects lineage tracing of Lgr5 and Bmi1 intestinal stem cell populations. Cell Stem Cell 12, 298–303 (2013).

    Google Scholar 

  33. Merritt, A. J. et al. The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res. 54, 614–617 (1994).

    Google Scholar 

  34. Wang, J. et al. p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome. Nat. Commun. https://doi.org/10.1038/s41467-023-44390-w (2024).

    Google Scholar 

  35. Diao, X. et al. Identification of oleoylethanolamide as an endogenous ligand for HIF-3α. Nat. Commun. https://doi.org/10.1038/s41467-022-30338-z (2022).

    Google Scholar 

  36. Taniguchi, C. M. et al. PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2. Sci. Transl. Med. 6, 236ra264 (2014).

    Google Scholar 

  37. Ravi, R. et al. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 14, 34–44 (2000).

    Google Scholar 

  38. Chen, D., Li, M., Luo, J. & Gu, W. Direct interactions between HIF-1α and Mdm2 modulate p53 function*. J. Biol. Chem. 278, 13595–13598 (2003).

    Google Scholar 

  39. Zhao, Y., Chen, X. Q. & Du, J. Z. Cellular adaptation to hypoxia and p53 transcription regulation. J. Zhejiang Univ. Sci. B 10, 404–410 (2009).

    Google Scholar 

  40. Mahe, M. M. et al. Establishment of gastrointestinal epithelial organoids. Curr. Protoc. Mouse Biol. 3, 217–240 (2013).

    Google Scholar 

  41. Qu, M. et al. Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration. Cell Res. 31, 259–271 (2021).

    Google Scholar 

  42. Li, M. et al. Vanillin derivative VND3207 activates DNA-PKcs conferring protection against radiation-induced intestinal epithelial cells injury in vitro and in vivo. Toxicol. Appl. Pharmacol. 387, 114855 (2020).

    Google Scholar 

Download references

Acknowledgements

We thank Professor Yuwen Cong for his generous gift of Lgr5-EGFP-IRES-CreERT2 mice. We also thank Goulin Xiong and Yin Xu for their technical assistance in experiments. The authors declare no use of Artificial Intelligence in this study.

Funding

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes
  1. Jiwei Zhao, Chunan Zhao & Xing Shen

    Present address: Academy of Military Medical Sciences, Beijing, 100850, China

  2. These authors contributed equally: Jiwei Zhao, Chunan Zhao and Xing Shen.

Authors and Affiliations

  1. Academy of Military Medical Sciences, Beijing, 100850, China

    Ying Jiang, Xun Wang, Aoqiang Ji, Xuewen Zhang, Shuang Xing, He Xiao & Zuyin Yu

  2. Department of Gastroenterology and Hepatology, First Medical Center, Chinese PLA General Hospital, Beijing, 100583, China

    Jiwei Zhao & Gang Sun

Authors
  1. Jiwei Zhao
    View author publications

    Search author on:PubMed Google Scholar

  2. Chunan Zhao
    View author publications

    Search author on:PubMed Google Scholar

  3. Xing Shen
    View author publications

    Search author on:PubMed Google Scholar

  4. Ying Jiang
    View author publications

    Search author on:PubMed Google Scholar

  5. Xun Wang
    View author publications

    Search author on:PubMed Google Scholar

  6. Aoqiang Ji
    View author publications

    Search author on:PubMed Google Scholar

  7. Xuewen Zhang
    View author publications

    Search author on:PubMed Google Scholar

  8. Shuang Xing
    View author publications

    Search author on:PubMed Google Scholar

  9. Gang Sun
    View author publications

    Search author on:PubMed Google Scholar

  10. He Xiao
    View author publications

    Search author on:PubMed Google Scholar

  11. Zuyin Yu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Ying Jiang and Xing Shen designed this study and conducted the main analysis. Jiwei Zhao, Chunan Zhao, Ying Jiang, Xing Shen, Aoqiang Ji and Xun Wang performed the experiments. Chunan Zhao wrote and edited the manuscript. Zuyin Yu, Gang Sun, Shuang Xing and Yuwen Cong provided additional expertise. Xing Shen, He Xiao, Zuyin Yu reviewed and edited the article. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Gang Sun, He Xiao or Zuyin Yu.

Ethics declarations

Competing interests

There are no ethical/legal conflicts involved in the article.

Ethics approval

The research was carried out in accordance with the approval of the ethics committee. Studies involving animal experiment were approved by the Institutional Animal Care and Use Committee of the Beijing Institute of Radiation Medicine. The approval project title is "Mechanism Study of Propylene Glycol in the Prevention and Treatment of Intestinal Acute Radiation Syndrome”. The permit number is “Ethics Review Approval no. IACUC-DWZX-2020–599″, which issued at April 15, 2025. All protocols followed are compliant with specific ethical regulations.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1206 kb) (download PDF )

Supplementary file1 (DOCX 1206 kb) (download DOCX )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, J., Zhao, C., Shen, X. et al. 1,2-propanediol ameliorated radiation-induced intestinal injury in mice. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43614-5

Download citation

  • Received: 07 October 2025

  • Accepted: 05 March 2026

  • Published: 11 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-43614-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer