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Increase in wound breaking strength in rats in the presence of positively charged dextran beads correlates with an increase in endogenous transforming growth factor‐β1 and its receptor TGF‐βRI in close proximity to the wound
Author(s) -
Connors David,
Gies David,
Lin Herrick,
Gruskin Elliott,
Mustoe Thomas A,
Tawil Nabil J
Publication year - 2000
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.2000.00292.x
Subject(s) - transforming growth factor , receptor , downregulation and upregulation , stimulation , growth factor , transforming growth factor beta , immunohistochemistry , andrology , endocrinology , medicine , chemistry , biology , biochemistry , gene
We have previously shown that positively charged beads (DEAE A25) increase wound breaking strength in linear incisions in rats and nonhuman primates at days 10–14 post‐wounding. The increased wound strength may result in part from a stimulation of cells adjacent to the DEAE A25 beads to produce growth factors important for wound healing. In this report, we investigate this hypothesis by comparing the relative expression levels of transforming growth factor‐β1 and its receptor transforming growth factor‐β receptor type I in DEAE A25‐treated and contralateral untreated rat linear incisions. DEAE A25‐treated incisions were stronger than untreated control wounds at 3 days post‐wounding, and the difference in breaking strength reached statistical significance at days 5, 7 and 10. Immunohistochemical analysis revealed a significant increase in transforming growth factor‐β1 and transforming growth factor‐β receptor type I expression in DEAE A25‐treated incisions, up to 7 days post‐wounding, as compared to untreated control wounds. FACS analysis revealed that macrophage cell lines exposed to DEAE A25 in vitro upregulate transforming growth factor‐β1 and transforming growth factor‐β receptor type I expression by 2–3 fold. Therefore, the increase in expression of transforming growth factor‐β1 and transforming growth factor‐β receptor type I in DEAE A25‐treated incisions may be due to an increase in the concentration of macrophages adjacent to DEAE A25 beads, as well as the stimulation of individual macrophages to produce greater amounts of transforming growth factor‐β1 and transforming growth factor‐β receptor type I. This study also supports the significance of transforming growth factor‐β1 in wound healing.