Osteopontin Knockout Does Not Influence the Severity of Rectal Damage in a Preclinical Model of Radiation Proctitis in Mice

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2015 Jan 12

PMID 25577272

Citations 1

Authors

Karl Blirando

Elodie Mintet

Valerie Buard

Jean-Christophe Sabourin

Marc Benderitter

Fabien Milliat

Agnes Francois

Affiliations

Soon will be listed here.

Abstract

Background: Radiation damage to the normal gut is a dose-limiting factor in the application of radiation therapy to treat abdominal and pelvic cancers. All tissue cell types react in concert to orchestrate an acute inflammatory reaction followed by a delayed chronic scarring process. Osteopontin (OPN) is a matricellular protein known to be involved in various physiological but also pathological processes such as tissue inflammation and fibrosis.

Aims: The aim of our study was to determine whether OPN knockout influences the severity of radiation proctitis and to investigate the role of OPN in the development of radiation-induced gut damage.

Results: Here we show that human radiation proctitis is associated with increased immunostaining of the intracellular and extracellular/matrix-linked isoforms of OPN. Moreover, endothelial cells in vitro and rectal tissue in a preclinical model of radiation proctitis in mice both respond to radiation exposure by a sustained increase in OPN mRNA and protein levels. Genetic deficiency of OPN did not influence radiation-induced rectal damage and was associated with significantly decreased animal survival. The acute and late radiation injury scores were similar in OPN-null mice compared with their control littermates.

Conclusion: This study shows that in our model and given the pleiotropic actions of OPN in tissue inflammation and fibrosis, further studies are necessary to understand the precise roles of OPN in radiation-induced proctitis and to determine whether OPN is a useful therapeutic tool in prevention of radiation-induced intestinal tissue injury.

Citing Articles

Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis.

Li Y, Ding Q, Gao J, Li C, Hou P, Xu J Sci Rep. 2022; 12(1):14116.

PMID: 35982137 PMC: 9388498. DOI: 10.1038/s41598-022-17981-8.

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