Objectives: 

Proper skin wound repair requires a highly organized combination of processes including re-epithelization, connective tissue contraction and angiogenesis. Endoglin is a transmembrane glycoprotein known to modulate cellular responses to TGF-beta and expressed in endothelium, skin keratinocytes and in tissues undergoing repairing (Lopez-Novoa and Bernabeu, Am J Physiol 299:H959-H974,2010). The purpose of our study was to assess the role of endoglin on wound healing.

Materials: 

Studies were performed in endoglin haploinsufficient (Eng+/– ) and WT (Eng+/+) female mice (4-6 months). Wounds were made on the back of the mouse and every two days wounds borders were drawn on a transparent film and wound areas calculated by image analysis software. The time at which wounds are closed at 50% (half closing time; HCT), was calculated using the individual healing curves.

Results: 

In Eng+/+ mice, wound was completely closed after 12 days while in Eng+/­ it occurred 1 or 2 days later. The largest differences were observed the first days after wounding: at day 4, i.e. remaining wound area was 42 ± 2 % in Eng+/+ mice, compared with 60 ± 2% in Eng+/­ mice (P<0.01). Endoglin expression increased in wounded skin reaching maximal values 4 days after wounding, and then decreasing. Calculated HTC was higher in Eng+/­ (4.2 ± 0.2 days) than in Eng+/+ mice (3.2 ± 0.2 days; P<0.01). Keratinocytes in healing area of Eng+/+ mice expressed Ki67, a proliferation marker, whereas this expression was almost negligible in Eng+/­ mice. Liposomal delivery of endoglin c-DNA to the wounds significantly accelerated wound closure in Eng+/­ mice without effect in Eng+/+ mice. Administration of L-NAME significantly delayed wound healing in Eng+/+ mice, with minimal effect in Eng+/­ mice, whereas administration of the NO donor LA-803 accelerated healing in Eng+/­, with no effect in Eng+/+ mice.

Conclusions: 

These results demonstrate that endoglin has an important role in early phases of wound healing process at least partly explained by the regulation of NO bioavailability and keratinocyte proliferation.