title: Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality.
abstract: Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT1R), has been associated with impaired wound healing, suggesting a critical role for AT1R in this repair process. Biological functions of angiotensin type 2 receptors (AT2R) are less studied. We investigated effects of genetically disrupting AT2R on rate and quality of wound healing. Our results suggest that AT2R effects on rate of wound closure depends on the phase of wound healing. We observed delayed healing during early phase of wound healing (inflammation). An accelerated healing rate was seen during later stages (proliferation and remodeling). By day 12, fifty percent of AT2R(-/-) mice had complete wound closure as compared to none in either C57/BL6 or AT1R(-/-) mice. There was a significant increase in AT1R, TGFβ1 and TGFβ2 expression during the proliferative and remodeling phases in AT2R(-/-) mice. Despite the accelerated closure rate, AT2R(-/-) mice had more fragile healed skin. Our results suggest that in the absence of AT2R, wound healing rate is accelerated, but yielded worse skin quality. Elucidating the contribution of both of the angiotensin receptors may help fine tune future intervention aimed at wound repair in older individuals.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Mahya
authors.initials: M
authors.lastname: Faghih
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Sayed M
authors.initials: SM
authors.lastname: Hosseini
authors.affiliation: Cell Biology Imaging Facility, Johns Hopkins University School of Medicine Baltimore, MD 21224, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Smith
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Amir Mehdi
authors.initials: AM
authors.lastname: Ansari
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Lay
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Ali Karim
authors.initials: AK
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Tedashi
authors.initials: T
authors.lastname: Inagami
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Guy P
authors.initials: GP
authors.lastname: Marti
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abadir
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta
keywords: AT1R; AT2R; Angiotensin; TGF