Altered in vitro immune response to hypoxia-treated normal peritoneal fibroblasts

Alpay, Zeynep; Özgönenel, Melike; Savaşan, Süreyya; Buck, Steven; Saed, Ghassan M.; Diamond, Michael P.

doi:10.1016/j.fertnstert.2006.07.1495

Cited by 9 publications

(7 citation statements)

References 15 publications

(16 reference statements)

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“…We have shown that exposure of normal peritoneal fibroblasts to hypoxia irreversibly induces TGF-b1 and type I collagen expression to levels seen in adhesion fibroblasts. 55,56 Similarly, the stimulatory effect of hypoxia on procollagen messenger RNA (mRNA) levels in fibroblast monolayers was diminished by antibodies to TGF-b1. 57 Transforming growth factor-b1 is a major profibrotic factor and has been described as a direct inductor of the myofibroblastic differentiation by controlling a-smooth muscle cell actin expression both in vitro 58 and in vivo 59 ( Figure 2).…”

Section: Tissue Injury Hypoxia Oxidative Stress and Transcription mentioning

confidence: 99%

Advances in the Pathogenesis of Adhesion Development: The Role of Oxidative Stress

et al. 2014

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Over the past several years, there has been increasing recognition that pathogenesis of adhesion development includes significant contributions of hypoxia induced at the site of surgery, the resulting oxidative stress, and the subsequent free radical production. Mitochondrial dysfunction generated by surgically induced tissue hypoxia and inflammation can lead to the production of reactive oxygen and nitrogen species as well as antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase which when optimal have the potential to abrogate mitochondrial dysfunction and oxidative stress, preventing the cascade of events leading to the development of adhesions in injured peritoneum. There is a significant cross talk between the several processes leading to whether or not adhesions would eventually develop. Several of these processes present avenues for the development of measures that can help in abrogating adhesion formation or reformation after intraabdominal surgery.

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Section: Tissue Injury Hypoxia Oxidative Stress and Transcription mentioning

confidence: 99%

Advances in the Pathogenesis of Adhesion Development: The Role of Oxidative Stress

et al. 2014

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“…We have demonstrated that hypoxia irreversibly increased the adhesion phenotype markers, specifically TGF-b1 and type I collagen [Saed et al 2004b;Alpay et al 2007]. The mechanism by which hypoxia irreversibly induces the adhesion phenotype is not fully understood.…”

Section: Introductionmentioning

confidence: 97%

Lycopene, a powerful antioxidant, significantly reduces the development of the adhesion phenotype

Fletcher

Awonuga

Saed

et al. 2013

Systems Biology in Reproductive Medicine

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Postoperative adhesions are a common medical complication of gynecologic and other pelvic surgeries resulting in persistent pelvic pain, obstruction of the intestines, and even infertility. The molecular mechanisms of postoperative adhesion development remain to be elucidated. We have recently described a role for reactive oxygen species, specifically superoxide, in the development of postoperative adhesions. In this study, we sought to determine whether lycopene, a potent antioxidant, reduces markers characteristic of the adhesion phenotype. Primary fibroblast cultures from normal peritoneum and adhesion tissues were utilized to determine mRNA levels of adhesion phenotype markers type I collagen, transforming growth factor-beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) in response to lycopene (24 hours, 10 μM) treatment. There was a 2 (p < 0.003), 4.7 (p < 0.004), and 1.6 fold (p < 0.004) increase in mRNA levels of type I collagen, TGF-β1, and VEGF, respectively, in adhesion as compared to normal peritoneal fibroblasts. Lycopene treatment led to a 6.8 and a 12.4 fold decrease in type I collagen mRNA levels, in normal peritoneal and adhesion fibroblasts, respectively (p < 0.005). Lycopene treatment led to a 4.2 (p < 0.03) and a 4.6 (p < 0.05) fold decrease in VEGF mRNA levels, in normal peritoneal and adhesion fibroblasts, respectively. Lycopene treatment led to a 7.0 fold decrease in TGF-β1 mRNA levels, in adhesion fibroblasts (p < 0.03). A 1.9 fold decrease in TGF-β1 mRNA was observed in normal peritoneal fibroblasts in response to treatment, although it was not significant. Lycopene substantially reduced levels of adhesion phenotype markers in normal peritoneal and adhesion fibroblasts and whether it will reduce postoperative adhesions needs to be further investigated.

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“…Type I collagen synthesis has been shown to be crucially dependent on the availability of molecular oxygen in tissue culture, animal, and human wound healing experiments [8,9]. Moreover, exposure of normal peritoneal fibroblasts to hypoxia irreversibly induces TGF-β1 and type I collagen to levels seen in adhesion fibroblasts [4,10]. However, the mechanism by which hypoxia induces the adhesion phenotype is not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-generated superoxide induces the development of the adhesion phenotype

Fletcher

Jiang

Diamond

et al. 2008

Free Radical Biology and Medicine

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Adhesion fibroblasts exhibit higher TGF-β1 and type I collagen expression as compared to normal peritoneal broblasts. Furthermore, exposure of normal peritoneal fibroblasts to hypoxia results in an irreversible increase in TGF-β1 and type I collagen. We postulated that the mechanism by which hypoxia induced the adhesion phenotype is through the production of superoxide either directly or through the formation of peroxynitrite. To test this hypothesis, normal peritoneal and adhesion fibroblasts were treated with superoxide dismutase (SOD), a superoxide scavenger, and xanthine/ xanthine oxidase, a superoxide-generating system, under normoxic and hypoxic conditions. Also, cells were treated with peroxynitrite. TGF-β1 and type I collagen expression was determined before and after all treatments using real-time RT/PCR. Hypoxia treatment resulted in a time-dependent increase in TGF-β1 and type I collagen mRNA levels in both normal peritoneal and adhesion fibroblasts. Similarly, treatment with xanthine oxidase, to endogenously generate superoxide, resulted in higher mRNA levels of TGF-β1 and type I collagen in both normal peritoneal and adhesion fibroblasts. In contrast, treatment with SOD, to scavenge endogenous superoxide, resulted in a decrease in TGF-β1 and type I collagen expression in adhesion fibroblasts to levels seen in normal peritoneal fibroblasts; no effect on the expression of these molecules was seen in normal peritoneal fibroblasts. Exposure to hypoxia in the presence of SOD had no effect on mRNA levels of TGF-β1 and type I collagen in either normal peritoneal or adhesion fibroblasts. Peroxynitrite treatment alone significantly induced both adhesion phenotype markers. In conclusion, hypoxia, through the production of superoxide, causes normal peritoneal fibroblasts to acquire the adhesion phenotype. Scavenging superoxide, even in the presence of hypoxia, prevented the development of the adhesion phenotype. These findings further support the central role of free radicals in the development of adhesions.

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Altered in vitro immune response to hypoxia-treated normal peritoneal fibroblasts

Cited by 9 publications

References 15 publications

Advances in the Pathogenesis of Adhesion Development: The Role of Oxidative Stress

Advances in the Pathogenesis of Adhesion Development: The Role of Oxidative Stress

Lycopene, a powerful antioxidant, significantly reduces the development of the adhesion phenotype

Hypoxia-generated superoxide induces the development of the adhesion phenotype

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