Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor
J. Clin. Invest. Gillian S. Ashcroft, et al. 111:1309 doi:10.1172/JCI16288 [Go to this article.]

Figure 2
Reduced circulating estrogen leads to enhanced local MIF expression. (a–c) Inflammatory cells and endothelium stained for MIF at day 7 after wounding (b, green arrows indicate endothelial cells). Inflammatory cell staining (arrows) for MIF was increased in day-7 wounds of OVX mice (b) as compared with their intact littermates (a). Estrogen (Es) replacement in wild-type OVX mice resulted in a marked reduction in MIF levels (c). All scale bars represent 20 μm. (d) MIF protein levels increased at day 3 (as compared with normal skin, which is scored as 0) and declined by day 14 in the wild-type mice (Western blot, lower panel), with significantly increased levels from days 7–14 in the OVX mice. Results represent medians (black lines across boxes), boxes represent interquartile ranges, and the bars extending from the boxes indicate the highest and lowest values (n = 4, *P < 0.05). Estrogen replacement in OVX mice reversed this increase in MIF. This temporal pattern was confirmed by Western blotting (d, lower panel). By RNase protection assay, MIF mRNA expression peaked at day 3 (e) and had decreased to basal levels by day 14 after wounding in wild-type intact mice. By contrast, MIF expression was more strongly upregulated from days 3–14 after wounding in the wild-type OVX mice. Normal skin is scored as 0, and the housekeeping gene is denoted by L32. For both RNA and protein analyses, four mice per time point were used.