Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin

Abstract

Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.

Radiotherapy and wound healing: Principles, management and prospects (Review)

“…the impact that growth factors and cytokines have in radiationinduced wound healing disorders is obvious. Further studies are necessary, but in the last few years it has become clear that there is an important and direct genetic component (74)(75)(76).…”

Accidental Radiogenic Ulcer of the Fingers in an Industrial Setting

“…Basically a reduction in some of the acute and delayed radiogenic damage is expected by downregulating transforming growth factor ß. A reduction in tenascin [7] and collagen synthesis [8][9][10] may be targeted while activating metalloproteinases. IFN-Á and pentoxifylline combined with ·-tocopherol have been reported to be other promising approaches [2][3][4][11][12][13][14].…”

Low Level Energy Photodynamic Therapy for Skin Processes and Regeneration

“…UV radiation induces MMP synthesis in human skin, and the destruction of collagen mediated by MMP counts mostly by the damage in connective tissue with photoaging [69]. It suggests that not only the synthesis of proteins in the ECM, but also their degradation is increased in irradiated skin [39].…”

“…As collagen is the main structural protein and composes 70-80% of the skin dry weight, the modulation of the collagen metabolism in the skin by therapeutic irradiation has clinical importance. The skin collagen synthesized by fibroblasts comprises 80-85% of type I collagen and 10-15% of type III collagen [39]. Type I collagen is easily visualized by optical microscopy after Picrosirius Red stain method as long red fibers.…”