Document Detail


Plasminogen activator inhibitor-I-related regulation of procollagen I (alpha1 and alpha2) by antitransforming growth factor-beta1 treatment during radiation-impaired wound healing.
MedLine Citation:
PMID:  16377416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Plasminogen activator inhibitor (PAI)-1 mediates transforming growth factor-beta1 (TGF-beta1)-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-beta1 treatment specifically inhibits alpha(I)-procollagen synthesis. We used an experimental wound healing study to address anti-TGF-beta1-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-beta1 treatment. On the 14th postoperative day, skin samples were processed for fibroblast culture, in situ hybridization for TGF-beta1, immunohistochemistry, and immunoblotting for PAI-1, alpha1/alpha2(I)-procollagen. RESULTS: Anti-TGF-beta1 significantly reduced TGF-beta1 mRNA (p < 0.05) and PAI-1 expression (p < 0.05). Anti-TGF-beta1 treatment in vivo significantly reduced alpha1(I)-procollagen protein (p < 0.05) and the number of expressing cells (p < 0.05) in contrast to significantly increased (p < 0.05) alpha2(I)-procollagen expression. CONCLUSION: These results emphasize anti-TGF-beta1 treatment to reduce radiation-induced fibrosis by decreasing alpha1(I)-procollagen synthesis in vivo. alpha1(I)-procollagen and alpha2(I)-procollagen might be differentially regulated by anti-TGF-beta1 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-beta1 treatment.
Authors:
Stefan Schultze-Mosgau; Jürgen Kopp; Michael Thorwarth; Franz Rödel; Ivan Melnychenko; Gerhard G Grabenbauer; Kerstin Amann; Falk Wehrhan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  64     ISSN:  0360-3016     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-26     Completed Date:  2006-03-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  280-8     Citation Subset:  IM    
Affiliation:
Department of Oral and Maxillofacial Surgery/Plastic Surgery, Freidrich-Schiller-University of Jena, Jena, Germany. stefan.schultze-mosgau@med.uni-jena.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Collagen Type I / biosynthesis*
Fibroblasts / metabolism,  radiation effects
Male
Plasminogen Activator Inhibitor 1 / metabolism,  physiology*
RNA, Messenger / biosynthesis
Radiation Injuries / prevention & control
Rats
Rats, Wistar
Surgical Flaps / physiology
Transforming Growth Factor beta / antagonists & inhibitors*,  immunology
Transforming Growth Factor beta1
Wound Healing*
Chemical
Reg. No./Substance:
0/Collagen Type I; 0/Plasminogen Activator Inhibitor 1; 0/RNA, Messenger; 0/Tgfb1 protein, rat; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1

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