The Impact of Smad3 Loss of Function on TGF-β Signaling and Radiation-Induced Capsular Contracture
- 1 June 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Plastic and Reconstructive Surgery
- Vol. 127 (6), 2263-2269
- https://doi.org/10.1097/prs.0b013e3182131bea
Abstract
Background: Capsular contracture remains a major problem following prosthetic breast implantation, especially in patients undergoing irradiation. Recent studies suggest that such radiation injuries are a cascading process of cytokine activation, with transforming growth factor (TGF)-β acting as the “master switch.” Because TGF-β signals through phosphorylation of Smad3, a plausible approach to abate TGF-β–induced capsular contracture would be to interrupt Smad3 signaling. To test this hypothesis, capsular contracture formation in wild-type and Smad3 knockout mice was compared using micro–computed tomographic and histologic examination. Methods: On day 0, 48 mice were implanted with bilateral silicone gel implants. Postoperatively, animals were imaged using live-scan micro–computed tomographic scanning. Animals in the radiation arm then received a 10-Gy directed radiation dose. On postoperative days 21, 28, 35, and 42, animals were imaged again. Histologic evaluation was performed at necropsy. Results: Irradiated implants in the wild-type mice demonstrated shape and contour deformation on micro–computed tomographic scanning beginning on postoperative day 21 and progressing through day 42. Conversely, micro–computed tomographic scanning of irradiated implants in knockout mice demonstrated few changes from day 0 through day 42. Corresponding histologic specimens from wild-type mice demonstrated irregular capsules composed of disorganized collagen that became thicker from day 21 to day 42. Irradiated knockout specimen maintained thin capsules from day 21 through day 42. Conclusions: In this work, inhibiting TGF-β signaling led to a reduction in radiation-induced capsular contracture as measured by micro–computed tomographic and histologic evaluation. The results of this study suggest a promising target for the prevention of capsular contracture through the development of anti-Smad3/TGF-β–based therapies.Keywords
This publication has 27 references indexed in Scilit:
- Radiation Therapy and Breast Reconstruction: A Critical Review of the LiteraturePlastic and Reconstructive Surgery, 2009
- Pilot Study of Association of Bacteria on Breast Implants with Capsular ContractureJournal of Clinical Microbiology, 2009
- Incidence of severe capsular contracture following implant-based immediate breast reconstruction with or without postoperative chest wall radiotherapy using 40 Gray in 15 fractionsRadiotherapy and Oncology, 2009
- Capsular Contracture: What is It? What Causes It? How Can It Be Prevented and Managed?Clinics in Plastic Surgery, 2009
- Relationship of Incision Choice to Capsular ContractureAesthetic Plastic Surgery, 2007
- Histologic Analysis of Zafirlukast’s Effect on Capsule Formation Around Silicone ImplantsAesthetic Plastic Surgery, 2007
- Modification of Cysteinyl Leukotriene Receptor Expression in Capsular ContractureAnnals of Plastic Surgery, 2007
- Radiotherapy and immediate two-stage breast reconstruction with a tissue expander and implant: Complications and esthetic resultsInternational Journal of Radiation Oncology*Biology*Physics, 2003
- Staged Breast Reconstruction with Saline-Filled Implants in the Irradiated Breast: Recent Trends and Therapeutic ImplicationsPlastic & Reconstructive Surgery, 2000
- Radiation Therapy as a Cause of Capsular ContractureAnnals of Plastic Surgery, 1994