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FIBCD1 ameliorates weight loss in chemotherapy-induced murine mucositis

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Abstract

Purpose

Chemotherapy-induced gastrointestinal toxicity is a common adverse event during chemotherapeutic treatment. No uniformly applicable strategies exist to predict, prevent, or treat gastrointestinal toxicity. Thus, a goal of mucositis research is to identify targets for therapeutic interventions and individualized risk prediction. Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane protein expressed in human intestinal epithelial cells with functions in the innate immune system. Previous observations have shown that FIBCD1 ameliorates dextran sulfate sodium (DSS)–induced intestinal inflammation in vivo. We evaluated the effect of FIBCD1 in a murine model of chemotherapy-induced gastrointestinal toxicity and inflammation.

Methods

Transgenic (Tg) mice overexpressing FIBCD1 in the intestinal epithelium (Fibcd1Tg) and wild-type (WT) littermates (C57BL/6N) were randomized to receive an intraperitoneal injection of doxorubicin 20 mg/kg or saline and were terminated 2 or 7 days after the injection. Gastrointestinal toxicity was evaluated by weight change, intestinal length, villus height/crypt depth, and histological mucositis score. Expression of inflammatory markers (IL-6, IL-1β, and Tnfα) was measured by quantitative real-time PCR in intestinal tissue samples.

Results

Following doxorubicin treatment, WT mice exhibited an increased weight loss compared with Tg littermates (p < 0.001). No differences between genotypes were seen in mucositis score, intestinal length, villus height/crypt depth, or IL-6, IL-1β, and Tnfα expression.

Conclusion

Our findings suggest that FIBCD1 could ameliorate chemotherapy-induced gastrointestinal toxicity by reducing weight loss; however, the mechanism of this possible protective effect remains to be defined warranting additional investigations.

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Acknowledgments

We gratefully thank the Department of Pathology at Odense University Hospital, Odense, Denmark, for performing the histological analyses.

Funding

This work was supported by a research grant from The Danish Child Cancer Foundation.

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Authors and Affiliations

  1. Hans Christian Andersen Children’s Hospital, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense C, Denmark

    Maria C. E. Andersen, Malene W. Johansen, Steffen Husby & Mathias Rathe

  2. Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark

    Maria C. E. Andersen, Malene W. Johansen, Thomas Nissen, Anders B. Nexoe, Grith L. Sorensen, Uffe Holmskov, Anders Schlosser & Jesper B. Moeller

  3. Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark

    Anders B. Nexoe

  4. Department of Pathology, Odense University Hospital, Odense, Denmark

    Gunvor I. Madsen

  5. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Steffen Husby & Mathias Rathe

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  1. Maria C. E. Andersen
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Correspondence to Mathias Rathe.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Danish National Committee on Animal Experimentation, J. no. 2017-15-0201-01385). This manuscript was prepared in accordance with the ARRIVE guidelines [34].

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Andersen, M.C.E., Johansen, M.W., Nissen, T. et al. FIBCD1 ameliorates weight loss in chemotherapy-induced murine mucositis. Support Care Cancer 29, 2415–2421 (2021). https://doi.org/10.1007/s00520-020-05762-w

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