This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, L. Articles by Mustoe, T. A. Search for Related Content PubMed PubMed Citation Articles by Wu, L. Articles by Mustoe, T. A.

(American Journal of Pathology. 1999;154:301-309.)
© 1999 American Society for Investigative Pathology

Animal Model

Transforming Growth Factor-ß1 Fails to Stimulate Wound Healing and Impairs Its Signal Transduction in an Aged Ischemic Ulcer Model

Importance of Oxygen and Age

Liancun Wu* , Yu-Ping Xia* , Sanford I. Roth , Elliott Gruskin and Thomas A. Mustoe*

From the Departments of Surgery* and Pathology Northwestern University Medical School, Chicago, Illinois, and the Department of Biotechnology, United States Surgical Corp., North Haven, Connecticut

Clinical trials of exogenous growth factors in treating chronic wounds have been less successful than expected. One possible explanation is that most studies used animal models of acute wounds in young animals, whereas most chronic wounds occur in elderly patients with tissue ischemia. We described an animal model of age- and ischemia-impaired wound healing and analyzed the wound-healing response as well as the transforming growth factor (TGF)-ß₁ effect in this model. Rabbits of increasing ages were made ischemic in the ear where dermal ulcers were created. Histological analysis showed that epithelium ingrowth and granulation tissue deposition were significantly impaired with increased age under ischemia. TGF-ß1 stimulated wound repair under both ischemic and non-ischemic conditions in young animals, although it showed no statistical difference in aged animals. Procollagen mRNA expression decreased under ischemic conditions and with aging. Neither TGF-ß1 nor procollagen 1(I) mRNA expression increased in response to TGF-ß1 treatment under ischemia in aged animals. Therefore, the wound-healing process is impaired additively by aging and ischemia. The lack of a wound-healing response to TGF-ß1 in aged ischemic wounds may play a role in the chronic wounds.

This article has been cited by other articles:

				M. Bujak, H. J. Kweon, K. Chatila, N. Li, G. Taffet, and N. G. Frangogiannis Aging-Related Defects Are Associated With Adverse Cardiac Remodeling in a Mouse Model of Reperfused Myocardial Infarction J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1384 - 1392. [Abstract] [Full Text] [PDF]

				M. Bujak and N. G. Frangogiannis The role of TGF-{beta} signaling in myocardial infarction and cardiac remodeling Cardiovasc Res, May 1, 2007; 74(2): 184 - 195. [Abstract] [Full Text] [PDF]

				J. Yamate, Y. Machida, M. Ide, M. Kuwamura, T. Kotani, O. Sawamoto, and J. LaMarre Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions Toxicol Pathol, February 1, 2005; 33(2): 207 - 217. [Abstract] [Full Text] [PDF]

				S. Coerper, C. Wicke, F. Pfeffer, G. Koveker, and H.-D. Becker Documentation of 7051 Chronic Wounds Using a New Computerized System Within a Network of Wound Care Centers Arch Surg, March 1, 2004; 139(3): 251 - 258. [Abstract] [Full Text] [PDF]

				S. R. Bonomo, J. D. Davidson, J. W. Tyrone, X. Lin, and T. A. Mustoe Enhancement of Wound Healing by Hyperbaric Oxygen and Transforming Growth Factor {beta}3 in a New Chronic Wound Model in Aged Rabbits Arch Surg, October 1, 2000; 135(10): 1148 - 1153. [Abstract] [Full Text] [PDF]