Plasminogen activator inhibitor-I-related regulation of procollagen I ({alpha}{sub 1} and {alpha}{sub 2}) by antitransforming growth factor-{beta}{sub 1} treatment during radiation-impaired wound healing

Journal Article · Sun Jan 01 04:00:00 EST 2006 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2005.0· OSTI ID:20788296

Schultze-Mosgau, Stefan ^[1]; Kopp, Juergen ^[2]; Thorwarth, Michael ^[3]; Roedel, Franz ^[4]; Melnychenko, Ivan ^[5]; Grabenbauer, Gerhard G ^[4]; Amann, Kerstin ^[6]; Wehrhan, Falk ^[3]

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1. Department of Oral and Maxillofacial Surgery/Plastic Surgery, University of Jena, Jena (Germany) and Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen (Germany)
2. Department of Plastic and Hand Surgery, University of Erlangen-Nuremberg, Erlangen (Germany)
3. Department of Oral and Maxillofacial Surgery/Plastic Surgery, University of Jena, Jena (Germany)
4. Department of Radiation Oncology, University of Erlangen-Nuremberg, Erlangen (Germany)
5. Department of Clinical and Experimental Pharmacology, University of Hamburg-Eppendorf, Hamburg (Germany)
6. Institute of Pathology, University of Erlangen-Nuremberg, Erlangen (Germany)

Purpose: Plasminogen activator inhibitor (PAI)-1 mediates transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1})-related signaling by stimulating collagen Type I synthesis in radiation-impaired wound healing. The regulation of {alpha}(I)-procollagen is contradictory in fibroblasts of different fibrotic lesions. It is not known whether anti-TGF-{beta}{sub 1} treatment specifically inhibits {alpha}(I)-procollagen synthesis. We used an experimental wound healing study to address anti-TGF-{beta}{sub 1}-associated influence on {alpha}(I)-procollagen synthesis. Methods and Materials: A free flap was transplanted into the preirradiated (40 Gy) or nonirradiated neck region of Wistar rats: Group 1 (n = 8) surgery alone; Group 2 (n = 14) irradiation and surgery; Group 3 (n = 8) irradiation and surgery and anti-TGF-{beta}{sub 1} treatment. On the 14th postoperative day, skin samples were processed for fibroblast culture, in situ hybridization for TGF-{beta}{sub 1}, immunohistochemistry, and immunoblotting for PAI-1, {alpha}{sub 1}/{alpha}{sub 2}(I)-procollagen. Results: Anti-TGF-{beta}{sub 1} significantly reduced TGF-{beta}{sub 1} mRNA (p < 0.05) and PAI-1 expression (p < 0.05). Anti-TGF-{beta}{sub 1} treatment in vivo significantly reduced {alpha}{sub 1}(I)-procollagen protein (p < 0.05) and the number of expressing cells (p < 0.05) in contrast to significantly increased (p < 0.05) {alpha}{sub 2}(I)-procollagen expression. Conclusion: These results emphasize anti-TGF-{beta}{sub 1} treatment to reduce radiation-induced fibrosis by decreasing {alpha}{sub 1}(I)-procollagen synthesis in vivo. {alpha}{sub 1}(I)-procollagen and {alpha}{sub 2}(I)-procollagen might be differentially regulated by anti-TGF-{beta}{sub 1} treatment. Increased TGF-{beta} signaling in irradiated skin fibroblasts seemed to be reversible, as shown by a reduction in PAI-1 expression after anti-TGF-{beta}{sub 1} treatment.

• OSTI ID: 20788296
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 64; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
COLLAGEN
FIBROBLASTS
FIBROSIS
GROWTH FACTORS
HEALING
IN VIVO
IN-SITU HYBRIDIZATION
IRRADIATION
NECK
PLASMINOGEN
RATS
SKIN
SURGERY
SYNTHESIS
WOUNDS