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Dynamic pathology for circulating free DNA in a dextran sodium sulfate colitis mouse model

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Abstract

Purpose

In sepsis, circulating free DNA (cf-DNA) is increased, and is a marker of severity and prognosis of septic patients. This study aimed to evaluate cf-DNA in a dextran sodium sulfate-induced colitis mouse model, and its clinical implications.

Methods

Dynamic pathology of the cecum wall in the DSS-induced colitis mouse model was analyzed using multiphoton microscopy (MPM). Plasma cf-DNA concentrations in colitis mouse were quantified using PicoGreen dsDNA Assay Kit. Plasma cf-DNA was also measured in 123 human ulcerative colitis (UC) patients [mean age: 35.9 years (3–75 years) with 20 pediatric patients] to assess its relationships with clinical severity and Matt’s grade.

Results

Real-time images of cf-DNA were detected in the colitis model. The amount of labeled cf-DNA in the circulation of the colitis mice group was significantly higher compared with that in the control group (P < 0.05). In human UC blood samples, plasma cf-DNA concentrations in UC patients were significantly positively correlated with the clinical severity of UC and Matt’s grade (P < 0.05, P < 0.05, respectively).

Conclusions

Using MPM, we observed and analyzed real-time images of cf-DNA in a colitis mouse model. Plasma cf-DNA is a potential non-invasive blood marker for reflecting clinical severity and mucosal damage in UC patients.

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Acknowledgments

This work was partly supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKENHI 25462771 to Y. K.). No additional external funding was received for this study.

Ethical standard

The experimental protocols of the in vivo studies were reviewed and approved by the Animal Care and Use Committee at the Mie University Graduate School of Medicine. Written informed consent was obtained from all of the patients or guardians enrolled in the study.

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Authors and Affiliations

  1. Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Yuhki Koike, Keiichi Uchida, Koji Tanaka, Shozo Ide, Kohei Otake, Yoshiki Okita, Mikihiro Inoue, Toshimitsu Araki & Masato Kusunoki

  2. Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Akira Mizoguchi

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  1. Yuhki Koike
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  2. Keiichi Uchida
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Correspondence to Yuhki Koike.

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Koike, Y., Uchida, K., Tanaka, K. et al. Dynamic pathology for circulating free DNA in a dextran sodium sulfate colitis mouse model. Pediatr Surg Int 30, 1199–1206 (2014). https://doi.org/10.1007/s00383-014-3607-6

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  • DOI: https://doi.org/10.1007/s00383-014-3607-6

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