Transforming growth factor ß1 and ß2 (TGFβ2 / TGFβ2) profile changes in previously irradiated free flap beds
- 20 December 2001
- journal article
- research article
- Published by Wiley in Head & Neck
- Vol. 24 (1), 33-41
- https://doi.org/10.1002/hed.10011
Abstract
Background Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes and the expression of cytokines involved in wound healing could be observed. These processes lead to a delayed healing of free flaps in the graft bed. The aim of the present experimental study was to analyze the expression profiles of transforming growth factor (activated TGFβ1, TGFβ2) and latency‐associated peptide (LAP) in the irradiated graft beds and the transition area between grafts and irradiated graft beds. Methods In Wistar rats (male, weight 300–500 g) undergoing preoperative irradiation of the neck region with 30 Gy (30 animals) and non‐irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The interval between irradiation and transplantation was 4 weeks. In each group on postoperative days 3, 7, 14, and 28, cytoplasmatic expression of activated TGFβ1, LAP, and TGFβ2 was analyzed by immunohistochemistry to determine labeling indices (positive stained cells/total cells). Results The success rate in graft beds irradiated with 30 Gy was 76% and in non‐irradiated graft beds was 86% (p = .02). In the graft beds irradiated with 30 Gy, there was an increased expression of activated TGFβ1 (range, 19.0–33.0), LAP (14.0–21.0), and TGFβ2 (3.0–19.5) together with obvious fibrosis. The expression was located in perivascular fibroblasts and endothelial cells. In contrast, a lower expression of activated TGFβ1 (11.0–21.0), LAP (1.0–8.0), and TGFβ2 (0.0–0.9) (p = .006) was observed in non‐irradiated graft beds. In the transition area between graft and irradiated graft bed, high expression of activated TGFβ1 (37.0), LAP (19.0), and TGFβ2 (16.7–33.4) was observed on the 3rd postoperative day in contrast to the transition area in non‐irradiated graft beds (activated TGFβ1 26.0, LAP 7.0, and TGFβ2 0.l). Conclusion The radiation induced, increased de novo synthesis of LAP, activation of TGFβ1, and increased expression of TGFβ2 may represent at least one mechanism for the increased fibrosis and wound healing disorders seen in irradiated tissues and in the transition area to graft tissue. The expression of TGFβ1, LAP, and TGFβ2 might possess prognostic value with regard to wound healing and fibrosis in previously irradiated graft beds. © 2002 John Wiley & Sons, Inc. Head Neck 24: 33–41, 2002.Keywords
Funding Information
- the Medical Faculty of Friedrich-Alexander University Erlangen-Nuremberg (Elan-Program Akt-Z.: 99.01.19.1)
This publication has 31 references indexed in Scilit:
- Histomorphometric analysis of irradiated recipient vessels and transplant vessels of free flaps in patients undergoing reconstruction after ablative surgeryInternational Journal of Oral & Maxillofacial Surgery, 2000
- Expression of Transforming Growth Factor Beta 1, 2, and 3 Proteins in KeloidsAnnals of Plastic Surgery, 1999
- The Effect of TGF-β on Keloid Fibroblast Proliferation and Collagen SynthesisPlastic and Reconstructive Surgery, 1996
- Expression of Transforming Growth Factor-β1 in Mouse Skin During the Acute Phase of Radiation DamageInternational Journal of Radiation Biology, 1995
- Accelerated Maturation in Prefabricated Flaps by Transforming Growth Factor-βAnnals of Plastic Surgery, 1993
- Temporal Modulation of TGF-β1 and β-Actin Gene Expression in Pig Skin and Muscular Fibrosis after Ionizing RadiationRadiation Research, 1993
- Keloid Fibroblasts Exhibit an Altered Response to TGF-βJournal of Investigative Dermatology, 1992
- Fibronectin Gene Transcription Is Enhanced in Abnormal Wound HealingJournal of Investigative Dermatology, 1992
- Microvascular transfer of anterior and posterior gracilis muscles in ratsMicrosurgery, 1991
- Inhibition of endothelial cell proliferation by type β-transforming growth factor: Interactions with acidic and basic fibroblast growth factorsBiochemical and Biophysical Research Communications, 1986