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An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.

ABSTRACT: Radiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT) with a crucial impact on the development of postoperative wound healing disorders (WHD). The grades of fibrosis vary between mild to severe depending on individual radiosensitivity. In this study, we have investigated the molecular pathways that influence RIF and have correlated data from immunohistochemistry (IHC) for von -Willebrand Factor (vWF) and from Real-Time Polymerase Chain Reaction (RT-PCR) concerning markers such as Transforming Growth Factor (TGF)-? 1, and vWF, with clinical data concerning the occurrence of WHD during follow-up.Expression profiles of the genes encoding TGF-? 1, vWF, and ?-procollagen (PC) were analyzed, by RT-PCR, in specimens from patients with (n?=?20; 25.6 %) and without (n?=?58; 74.4 %) a history of previous RT to the head and neck. Moreover, IHC against vWF was performed. Clinical data on the occurrence of cervical WHDs were analyzed and correlated.A statistically significant increase in the expression profiles of ?-PC and TGF-? 1 was observed in previously irradiated skin samples (occurrence of RT >91 days preoperatively). vWF showed a statistically significant increase in non-irradiated tissue. Moreover, analysis of expression profiles in patients with and without WHDs during follow-up was performed. IHC showed a reduced amount of vessels and structural changes in epidermal tissue post-RT.The expression of markers of fibrosis and angiogenesis was analyzed in order to gain insight into molecular pathways that account for structural changes in irradiated skin and that eventually lead to WHDs. The results are congruent with reports from the literature and are a possible starting point for further research, as anti-TGF-? 1 treatment, for example, could represent new therapeutic opportunities in the management of previously irradiated patients.

SUBMITTER: Koerdt S

PROVIDER: S-EPMC4578371 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.

Koerdt Steffen S Rohleder Nils H NH Rommel Niklas N Nobis Christopher C Stoeckelhuber Mechthild M Pigorsch Steffi S Duma Marciana-Nona MN Wolff Klaus-Dietrich KD Kesting Marco R MR

Radiation oncology (London, England) 20150922

<h4>Background</h4>Radiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT) with a crucial impact on the development of postoperative wound healing disorders (WHD). The grades of fibrosis vary between mild to severe depending on individual radiosensitivity. In this study, we have investigated the molecular pathways that influence RIF and have correlated data from immunohistochemistry (IHC) for von -Willebrand Factor (vWF) and from Real-Time Polymeras ...[more]

PMID: 26390925

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Project description:Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up-regulating angiogenesis as observed over multiple time points. This therapeutic approach may have potential application for clinical management of delayed and chronic wounds.

Dataset Information

An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.

Publications

An expression analysis of markers of radiation-induced skin fibrosis and angiogenesis in wound healing disorders of the head and neck.

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