ER-alpha agonist induces conversion of fibroblasts into myofibroblasts, while ER-beta agonist increases ECM production and wound tensile strength of healing skin wounds in ovariectomised rats

Abstract

Oestrogen deprivation is one of the major factors responsible for many age-related processes, including poor wound healing in women. Previously, it has been shown that oestrogens have a modulatory effect in different wound-healing models.

Therefore, in this study, the effect of selective oestrogen receptor (ER) agonists (PPT - ER-alpha agonist, DPN - ER-beta agonist) on excisional and incisional wound-healing models was compared in ovariectomised rats in vivo as well as on human dermal fibroblasts (HDF) and human umbilical endothelial cells (HUVEC) in vitro. In the in vivo study, 4 months after either ovariectomy or sham ovariectomy, Sprague-Dawley rats were randomly divided into four groups and subjected to two incisional and excisional wounds: (i) control sham operated, vehicle-treated; (ii) ovariectomised, vehicle-treated; (iii) ovariectomised, PPT treated; (iv) ovariectomised, DPN treated.

In the in vitro study, HDFs and HUVECs were used. After treatment with ER agonists, cells were processed for immunocytochemistry and gelatin zymography.

Our study shows that stimulation of ER-alpha leads to the differentiation of fibroblasts into myofibroblasts both in vivo and in vitro. On the other hand, the formation of extracellular matrix was more prominent, and wound tensile strength (TS) was increased when ER-beta was stimulated.

In contrast, stimulation of ER-alpha led to a more prominent increase in the expression of MMP-2 and decrease in wound T'S. New information is presented in this investigation concerning oestrogen replacement therapy (ERT) in different wound-healing models.

This study demonstrates that the ERT should be both wound and receptor-type specific.