title: Impaired wound repair in adult endoglin heterozygous mice associated with lower NO bioavailability.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Spanish National Research Council (CSIC), Autonomous University of Madrid (UAM), Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez-Gómez
authors.affiliation: Renal and Cardiovascular Physiopathology Unit, Instituto Reina Sofia de Investigación, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain; Molecular Structure and Function Program, Hospital for Sick Children, Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Jerkic
authors.affiliation: Renal and Cardiovascular Physiopathology Unit, Instituto Reina Sofia de Investigación, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Prieto
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Spanish National Research Council (CSIC), Autonomous University of Madrid (UAM), Madrid, Spain.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Del Castillo
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Spanish National Research Council (CSIC), Autonomous University of Madrid (UAM), Madrid, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Martín-Villar
authors.affiliation: Molecular Structure and Function Program, Hospital for Sick Children, Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Letarte
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
authors.affiliation: Renal and Cardiovascular Physiopathology Unit, Instituto Reina Sofia de Investigación, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pérez-Barriocanal
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Spanish National Research Council (CSIC), Autonomous University of Madrid (UAM), Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintanilla
authors.affiliation: Renal and Cardiovascular Physiopathology Unit, Instituto Reina Sofia de Investigación, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain. Electronic address: jmlnovoa@usal.es.
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
mesh_terms: D000367:Age Factors; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D049109:Cell Proliferation; D000071063:Endoglin; D004817:Epidermis / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006965:Hyperplasia; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002273:Carcinogens; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009569:Nitric Oxide; D013755:Tetradecanoylphorbol Acetate