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Erschienen in: Supportive Care in Cancer 11/2018

12.05.2018 | Original Article

Matrix metalloproteinase expression is altered in the small and large intestine following fractionated radiation in vivo

verfasst von: Romany L. Stansborough, Noor Al-Dasooqi, Emma H. Bateman, Joanne M. Bowen, Dorothy M. K. Keefe, Richard M. Logan, Ann S. J. Yeoh, Eric E. K. Yeoh, Andrea M. Stringer, Rachel J. Gibson

Erschienen in: Supportive Care in Cancer | Ausgabe 11/2018

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Abstract

Purpose

Radiotherapy-induced gut toxicity (RIGT) is associated with significant diarrhoea, pain and rectal bleeding. Matrix metalloproteinases (MMPs) have been reported to be involved in chemotherapy-induced gut toxicity and RIGT following single-dose irradiation in vivo. We therefore proposed MMPs would be involved in the pathobiology of RIGT following fractionated irradiation.

Methods

Dark Agouti rats were treated with fractionated radiation (3 × 2.5 Gy/week for 6 weeks). Rats were killed at 3, 6 and 15 weeks to represent acute and chronic toxicities. Sections of jejunum and colon were immunostained for MMP-1, MMP-2, MMP-9 and MMP-14. Relative mRNA expression in jejunum and colon was quantified by RT-PCR for MMP-1, MMP-2, MMP-9 and MMP-14. Western blotting was also conducted on jejunum and colon tissue collected at week 6 to determine protein levels of pro- and active MMP-2.

Results

MMP-2 total protein levels, determined by western blotting, significantly increased in both the jejunum (p = 0.0359) and the colon (p = 0.0134) 6 weeks into the fractionated radiation schedule. MMP-1, MMP-2, and MMP-14 mRNA expression significantly increased in the jejunum. MMP-2 mRNA expression was also significantly increased in the colon. Immunostaining of MMP-2 was observed to be increased in both crypt enterocytes and the lamina propria.

Conclusions

MMP-2 plays a role in the pathobiology of gastrointestinal toxicities following fractionated irradiation. Whilst MMP-1 and MMP-14 mRNA expression was increased, this occurred only in the jejunum, suggesting MMPs are differentially involved in RIGT depending on the intestinal region. Further studies are needed to elucidate the role these mediators play in the development and potentiation of RIGT.
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Metadaten
Titel
Matrix metalloproteinase expression is altered in the small and large intestine following fractionated radiation in vivo
verfasst von
Romany L. Stansborough
Noor Al-Dasooqi
Emma H. Bateman
Joanne M. Bowen
Dorothy M. K. Keefe
Richard M. Logan
Ann S. J. Yeoh
Eric E. K. Yeoh
Andrea M. Stringer
Rachel J. Gibson
Publikationsdatum
12.05.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Supportive Care in Cancer / Ausgabe 11/2018
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-018-4255-5

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