Long-Term Overproduction of Collagen in Radiation-Induced Fibrosis

Rémy, Jacques; Wegrowski, J; Créchet, Françoise; Martin, Michble; Daburon, F.

doi:10.2307/3577976

Cited by 79 publications

(33 citation statements)

References 21 publications

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“…20 Furthermore, these studies show that fibrotic lesion formation in different organs is characterized by similar pathways of collagen synthesis and accumulation. The Col1A2 promoter contains Smad binding elements that are necessary and sufficient to mediate the transcriptional responses induced by TGF-β.…”

Section: Discussionmentioning

confidence: 84%

Bladder Stromal Loss of Transforming Growth Factor Receptor II Decreases Fibrosis After Bladder Obstruction

et al. 2009

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Purpose Transforming growth factor-β is a potent stimulator of extracellular matrix production. Several studies show that loss of transforming growth factor-β signaling decreases kidney, liver and lung fibrosis. However, the role of transforming growth factor-β signaling in bladder fibrosis is not entirely understood. We investigated the effect of stromal loss of such signaling in mice after partial bladder outlet obstruction. Materials and Methods We performed partial bladder outlet obstruction by urethral ligation in 5-week-old female Tgfbr2colTKO mice. These mice were compared to WT mice with partial bladder outlet obstruction and to WT nonobstructed controls. After 4 weeks and before sacrifice urodynamics were performed. Bladder tissue was harvested, and p-Smad2 and collagen (Masson’s trichrome) staining were performed. Results Bladder compliance was increased in partially obstructed Tgfbr2colTKO mice and decreased in partially obstructed WT mice. The latter had increased smooth muscle hypertrophy and increased collagen deposition between smooth muscle bundles compared to those in Tgfbr2colTKO mice and nonobstructed controls. Transforming growth factor-β responsive collagen promoter activity was significantly decreased in Tgfbr2 knockout bladder stromal cells vs WT stromal cells. Conclusions Stromal loss of transforming growth factor-β signaling decreased collagen deposition after partial bladder outlet obstruction. In contrast to collagen production by recruited macrophages, stromal transforming growth factor-β signaling appears to be the primary source of fibrosis after partial bladder outlet obstruction. These findings further support the hypothesis that manipulating transforming growth factor-β signaling in bladder stromal cells would provide a future avenue for neuropathic bladder and bladder fibrosis treatment.

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Section: Discussionmentioning

confidence: 84%

Bladder Stromal Loss of Transforming Growth Factor Receptor II Decreases Fibrosis After Bladder Obstruction

et al. 2009

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“…It is well known that radiation changes are likely to start at the time of irradiation and progressively increase. 18,19 The current data showed that an increase in nerve density correlated with a longer time interval between pelvic irradiation and surgery.…”

Section: Discussionmentioning

confidence: 86%

Histologic Analysis of the Irradiated Anal Sphincter

Silva¹,

Berho²,

Wexner³

et al. 2003

Diseases of the Colon &Amp; Rectum

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Pelvic irradiation results in damage to the myenteric plexus of the internal anal sphincter of patients with rectal cancer; these alterations seem to be time-dependent. A trend toward increased collagen deposition also was observed. Together, these results provide a morphologic basis, which concurs to previously described physiologic and clinical alterations in the anal sphincter of patients irradiated for rectal cancer.

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“…Radiation rapidly and persistently alters the soluble and insoluble components of the ECM (Barcellos-Hoff et al 2005). In model systems, cells in the ECM such as fibroblasts, respond to IR by increasing the production or remodeling of collagen (type I and III) and fibronectin (Barcellos-Hoff 1993, Remy et al 1991. Fibroblasts isolated from post-radiation biopsies in patients with recurrent breast cancer produce dramatically increased levels of fibronectin (Brouty-Boye et al 1991).…”

Section: Discussionmentioning

confidence: 99%

alpha6 Integrin Cleavage: Sensitizing human prostate cancer to ionizing radiation

Pawar

Dougherty

Pennington

et al. 2007

International Journal of Radiation Biology

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Purpose-The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments.Material and methods-Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated noncleavable form of α6 integrin (PC3N-α6-RR). The resulting tumor growth before, during and after fractionated doses of IR (3 Gy × 10 days) was analyzed using the endpoints of tumor growth inhibition (T/C), tumor growth delay (T-C), tumor doubling time (Td) and tumor cell kill (Log 10 cell kill).Results-The T/C values were 36.1% and 39.5%, the T-C values were 20.5 days and 28.5 days and the Td values were 5.5 and 10.5 days for the irradiated PC3N-α6-WT and PC3N-α6-RR cells, respectively. The Log 10 was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 integrin as indicated by a significant increase in tumor growth inhibition, an increase in tumor growth delay, an increase in tumor doubling time and an increase in tumor cell kill.Conclusions-Blocking integrin cleavage in vivo may be efficacious for increasing the IR responsiveness of slow growing, pro-metastatic human prostate cancer.

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Long-Term Overproduction of Collagen in Radiation-Induced Fibrosis

Cited by 79 publications

References 21 publications

Bladder Stromal Loss of Transforming Growth Factor Receptor II Decreases Fibrosis After Bladder Obstruction

Bladder Stromal Loss of Transforming Growth Factor Receptor II Decreases Fibrosis After Bladder Obstruction

Histologic Analysis of the Irradiated Anal Sphincter

alpha6 Integrin Cleavage: Sensitizing human prostate cancer to ionizing radiation

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