Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

Möbius P, Preidl R, Weber M, Amann KU, Neukam FW, Wehrhan F (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Strahlentherapie und Onkologie Urban & Vogel

Abstract

Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y-box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region.DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively.DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels.Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

Authors with CRIS profile

Patrick Möbius Department of Oral and Cranio-Maxillofacial Surgery Raimund Preidl Department of Oral and Cranio-Maxillofacial Surgery Manuel Weber Department of Oral and Cranio-Maxillofacial Surgery Kerstin Ute Amann Professur für Nephropathologie Friedrich Wilhelm Neukam Medizinische Fakultät Falk Wehrhan Department of Oral and Cranio-Maxillofacial Surgery

How to cite

APA:

Möbius, P., Preidl, R., Weber, M., Amann, K.U., Neukam, F.W., & Wehrhan, F. (2017). Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region. Strahlentherapie und Onkologie. https://doi.org/10.1007/s00066-017-1192-z

MLA:

Möbius, Patrick, et al. "Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region." Strahlentherapie und Onkologie (2017).

BibTeX: Download