Transforming growth factor-beta 1 fails to stimulate wound healing and impairs its signal transduction in an aged ischemic ulcer model - Importance of oxygen and age
Lc. Wu et al., Transforming growth factor-beta 1 fails to stimulate wound healing and impairs its signal transduction in an aged ischemic ulcer model - Importance of oxygen and age, AM J PATH, 154(1), 1999, pp. 301-309
Citations number
61
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
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 c
hronic wounds occur in elderly patients with tissue ischemia. We described
an animal model of age- and ischemia-impaired wound healing and analyzed th
e wound-healing response as well as the transforming growth factor (TGF)-be
ta(1) effect in this model. Rabbits of increasing ages were made ischemic i
n the ear where dermal ulcers were created. Histological analysis showed th
at epithelium ingrowth and granulation tissue deposition were significantly
impaired with increased age under ischemia, TGF-beta 1 stimulated wound re
pair under both ischemic and non-ischemic conditions in young animals, alth
ough it showed no statistical difference in aged animals. Procollagen mRNA
expression decreased under ischemic conditions and with aging. Neither TGF-
beta 1 nor procollagen alpha 1(I) mRNA expression increased in response to
TGF-beta 1 treatment under ischemia in aged animals. Therefore, the wound-h
ealing process is impaired additively by aging and ischemia. The lack of a
wound-healing response to TGF-beta 1 in aged ischemic wounds may play a rol
e in the chronic mounds.