Is the loss of endothelial thrombomodulin involved in the mechanism of chronicity in late radiation enteropathy?

Radiothérapie : quelles orientations thérapeutiques contre les séquelles digestives ?

“…Ainsi, plus le taux de TM membranaire est faible, plus le taux de thrombine libre augmente et plus le phénotype vasculaire est pro-thrombotique. Le taux de TM est diminué dans la microvascularisation intestinale chez les patients atteints d'entérite radique chronique [18]. Les phases aiguë et tardive de l'entérite radique chez l'animal sont associées à des réductions de l'expression de la TM et à une augmentation de l'expression de PAR-1, un récepteur de la thrombine [19].…”

Current concepts in radiation enteritis and implications for future clinical trials

“…22 Pathologic examination of bowel specimens from patients who underwent surgery for radiation enteropathy showed an increased immunoreactivity of TGF-␤ in areas with vascular sclerosis and fibrotic areas of serosa and muscularis propria compared with patients who underwent surgery for other reasons. 23 …”

“…78 In another study with the same dose and frequency of IFN-␥, there also was a stabilization of visceral involvement. 79 A higher dose of IFN-␥ (150 mcg per day) induced a significant decrease in skin thickness compared with a lower dose (60 mcg per 17 Rat Intestines 0, 12 ISH Increased Wang et al 18 Rat Intestines 0, 12 CIA, IH Increased Hauer-Jensen et al 19 Rat Intestines 21 RTP, ISH Increased Zheng et al 20 Mouse Intestines 21 RTP, IH Inhibited by soluble TGF-␤ receptor Richter et al 23 Human Intestines NS IH Increased Bai et al 38 Rat Lungs 30 IH, ISH Increased Rube et al 39 Mouse Lungs 6, 12 IH, RTP Increased Rubin et al 43 Mouse Lungs 5 IH, ISH Increased Anscher et al 45 Human Lungs NS EIA Increased Randall and Coggle 50 Mouse Skin 50 PCR Increased Martin et al 51 Pig Skin 140 NBH, SBT, IF Increased Lefaix et al 55 Pig Skin 160 US, IH Inhibited by PTX and vit E Zhao et al 60 Rat Kidney 1-10 NBA Increased Robbins et al 61 Rat Kidney 10, 15, 20 IH Increased Zhao et al 62 Rat Kidney 1-10 WBA, LA Increased Datta et al 63 Rat Kidney 15 EIA Increased Seong et al 65 Rat Liver 25 IH Increased Geraci and Mariqno 66 Rat Liver 25 RH Increased Anscher et al 67 Rat Liver NS IH Increased TGF-␤: transforming growth factor beta; Gy: Gray; NS: not specified; IH: immunohistochemistry; RIS: radiation injury scoring; TBS: toluidine blue stain; ISH: in situ hybridization; CIA: computerized image analysis; RTP: reverse transcriptase polymerase; EIA: enzyme-linked immunosorbent assay; US: ultrasound; NBH: Northern blot hybridization; SBH: Southern blot hybridization; PCR: polymerase chain reaction; NBA: Northern blot analysis; WBA: Western blot analysis; LA: luciferase assay; RH: ribonucleic acid hybridization; PTX: pentoxifylline; vit E: vitamin E. day). 80 The beneficial effect of IFN-␥ on skin lesions also was reported in a randomized study: Mouth aperture and skin scores increased significantly in the treated group after 12 months of treatment with IFN-␥ (100 mcg per day).…”

Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease

“…7,8 Thrombomodulin (TM) is expressed on the surface of endothelial cells and mediates an anti-apoptotic signal via activation of protein C and cleavage of PAR-1. 9 Vessels of solid organ transplants undergoing acute rejection show depletion of endothelial TM, 10 and so did endothelial cells in radiation induced colitis 11 and inflammatory bowel disease. 12,13 However, so far, no histological studies on endothelial TM expression during GvHD have been reported.…”