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Recombinant adenovirus‐p21 attenuates proliferative responses associated with excessive scarring
Author(s) -
Gu Danling,
Atencio Isabella,
Kang David W.,
Looper L. David,
Ahmed C. M. I.,
Levy Alina,
Maneval Dan,
Zepeda Monica L.
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.00068.x
Subject(s) - bromodeoxyuridine , cell growth , granulation tissue , in vivo , immunohistochemistry , platelet derived growth factor receptor , microbiology and biotechnology , platelet derived growth factor , growth factor , wound healing , cancer research , biology , chemistry , immunology , receptor , biochemistry
Excessive cutaneous scarring is an important clinical disorder resulting in adverse tissue growth and function as well as undesirable cosmetic appearance. p21 WAF−1/Cip−1 is a cyclin‐dependent kinase inhibitor that blocks cell cycle progression and inhibits cell proliferation. We used a recombinant adenovirus containing the human p21 WAF−1/Cip−1 cDNA (rAd‐p21) to evaluate proliferative responses in skin models. In vitro dose–response studies using primary human dermal fibroblasts resulted in a dose‐dependent expression of p21 WAF−1/Cip−1 protein and a 3‐ to 80‐fold reduction in cell proliferation as measured by 5‐bromodeoxyuridine incorporation. Further, rAd‐p21 reduced type I procollagen production when compared to control virus. A rat polyvinyl alcohol sponge model was used to determine rAd‐p21 effects on granulation tissue formation in vivo. Sponges pretreated with a granulation tissue stimulator, rAd‐PDGF‐B and subsequently rAd‐p21 on a second injection, showed a p21 WAF−1/Cip−1 specific dose‐dependent decrease in percent granulation fill as the rAd‐p21 dose increased ( p < 0.001). Immunohistochemistry identified human p21 WAF−1/Cip−1 expression in sponges treated with rAd‐p21 5 days postinjection. Additionally, 5‐bromodeoxyuridine and Ki67 staining in sponges treated with rAd‐p21 showed a significant decrease in proliferation when compared to rAd‐platelet‐derived growth factor‐B alone or vehicle control groups ( p < 0.01). These data support the utility of p21 WAF−1/Cip−1 in targeting hyperproliferative disorders of the skin.