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Publication : Impaired wound repair in adult endoglin heterozygous mice associated with lower NO bioavailability.

First Author  Pérez-Gómez E Year  2014
Journal  J Invest Dermatol Volume  134
Issue  1 Pages  247-255
PubMed ID  23765132 Mgi Jnum  J:205076
Mgi Id  MGI:5543984 Doi  10.1038/jid.2013.263
Citation  Perez-Gomez E, et al. (2014) Impaired wound repair in adult endoglin heterozygous mice associated with lower NO bioavailability. J Invest Dermatol 134(1):247-55
abstractText  Endoglin (Eng) is a transmembrane glycoprotein that is mainly expressed in endothelial cells, but it is also present in the epidermis and skin appendages. To address the role of Eng in cutaneous wound healing, we compared the kinetics of reepithelialization in Eng heterozygous null (Eng(+/-)) mice and their normal littermates (Eng(+/+)) following skin wounds. The wound area was significantly larger in Eng(+/-) than in Eng(+/+) mice from 2 to 8 days after injury; overall wound closure was delayed by 1 to 2 days. In Eng(+/-) mice, keratinocytes at the wound edges exhibited impaired proliferation but were more migratory, as shown by their elongated morphology and increased keratin 17 expression. Inhibition of nitric oxide (NO) synthesis delayed healing in Eng(+/+) but not in Eng(+/-) mice. Administration of the NO donor LA-803 accelerated wound closure in Eng(+/-) mice, with no effect on normal littermates. The acute stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced Eng expression in mouse epidermal keratinocytes in vivo and in vitro associated with hyperproliferation. Similarly, the skin of Eng(+/-) mice failed to mount a hyperplastic response to acute stimulation with TPA. These results demonstrate an important involvement of Eng in wound healing that is associated with NO bioavailability.
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