No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
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No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis. / Nexoe, Anders B.; Pedersen, Andreas A.; von Huth, Sebastian; Sorensen, Grith L.; Holmskov, Uffe; Jiang, Ping Ping; Detlefsen, Sönke; Husby, Steffen; Rathe, Mathias.
In: Scientific Reports, Vol. 11, No. 1, 14687, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
AU - Nexoe, Anders B.
AU - Pedersen, Andreas A.
AU - von Huth, Sebastian
AU - Sorensen, Grith L.
AU - Holmskov, Uffe
AU - Jiang, Ping Ping
AU - Detlefsen, Sönke
AU - Husby, Steffen
AU - Rathe, Mathias
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Mucositis is a serious adverse effect of chemotherapeutic treatment. During intestinal mucositis, the mucosal barrier is compromised, increasing the risk of severe infections. Mucositis necessitates dose reduction or pauses in treatment, which affect the outcome of the treatment. Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger protein with effects on innate immunity and epithelial regeneration. We have previously shown that jejunal DMBT1 expression is increased in piglets during chemotherapeutic treatment. We hypothesized that DMBT1 ameliorates doxorubicin-induced mucositis. Individually-caged Dmbt1+/+ (WT) and Dmbt1−/− (KO) female mouse littermates received intraperitoneal injections of either doxorubicin or saline. They were euthanized after three (D3) or seven days (D7). Weight loss was monitored every day, and serum citrulline levels were measured at termination. Intestinal tissue was analyzed for the expression of DMBT1 and proinflammatory cytokines (IL-1β, IL-6, and TNF). Specimens from the small intestines and colon were scored for inflammation and epithelial and mucosal architecture changes. We detected no effect of DMBT1 on weight loss, serum citrulline levels, expression of proinflammatory cytokines, or histologic damage. We detected a significant increase in crypt depth in WT mice compared to that in KO mice on D3. In conclusion, DMBT1 does not affect doxorubicin-induced mucositis in mice.
AB - Mucositis is a serious adverse effect of chemotherapeutic treatment. During intestinal mucositis, the mucosal barrier is compromised, increasing the risk of severe infections. Mucositis necessitates dose reduction or pauses in treatment, which affect the outcome of the treatment. Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger protein with effects on innate immunity and epithelial regeneration. We have previously shown that jejunal DMBT1 expression is increased in piglets during chemotherapeutic treatment. We hypothesized that DMBT1 ameliorates doxorubicin-induced mucositis. Individually-caged Dmbt1+/+ (WT) and Dmbt1−/− (KO) female mouse littermates received intraperitoneal injections of either doxorubicin or saline. They were euthanized after three (D3) or seven days (D7). Weight loss was monitored every day, and serum citrulline levels were measured at termination. Intestinal tissue was analyzed for the expression of DMBT1 and proinflammatory cytokines (IL-1β, IL-6, and TNF). Specimens from the small intestines and colon were scored for inflammation and epithelial and mucosal architecture changes. We detected no effect of DMBT1 on weight loss, serum citrulline levels, expression of proinflammatory cytokines, or histologic damage. We detected a significant increase in crypt depth in WT mice compared to that in KO mice on D3. In conclusion, DMBT1 does not affect doxorubicin-induced mucositis in mice.
U2 - 10.1038/s41598-021-94076-w
DO - 10.1038/s41598-021-94076-w
M3 - Journal article
C2 - 34282203
AN - SCOPUS:85110799265
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 14687
ER -
ID: 275825936