Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression

Article Article scientifique Article Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression eng 2002 author Darby Ian A author Bisucci Teresa author Pittet Cuenod Brigitte Maud 114581 author Garbin Stefania 99830 author Gabbiani Giulio 24889 author Desmouliere Alexis Xavier Marie J. 22909 117-127 10.1002/path.1074 12081196 0022-3417 Previous studies have shown that covering granulation tissue of a full-thickness skin wound by a vascularized skin flap induces tissue remodeling, with a rapid loss of granulation tissue cells by apoptosis. In the present study, in situ hybridization has been used to examine mRNA expression for several factors that may be implicated in the apoptosis seen in this tissue. Skin wounds were made on the dorsal skin of 8-week-old rats. Ten days after wounding, skin flaps were created surgically and sutured over the granulation tissue. Tissue sections of granulation tissue from various times after addition of the skin flap were hybridized with 33P-labelled cRNA probes for transforming growth factor-beta1 (TGF-beta1), beta-inducible gene H3 (beta-ig-h3), alpha1 (1) procollagen, alpha-smooth muscle actin, matrix metalloproteinase-13 (MMP-13) and -2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), and inducible nitric oxide synthase (iNOS). Control granulation tissue prior to addition of the skin flap showed high levels of TGF-beta1, beta-ig-h3, alpha1 (1) procollagen, alpha-smooth muscle actin, and TIMP-1 expression. MMP-13, MMP-2, and iNOS mRNA were low in 10-day granulation tissue. Addition of a skin flap resulted in a decrease in the expression of TGF-beta1, beta-ig-h3, alpha1 (I) procollagen, alpha-smooth muscle actin, and TIMP-1, but increased expression of MMP-13 and MMP-2. Similarly, an increase in iNOS mRNA expression was observed in the granulation tissue after addition of the skin flap. Addition of a vascularized skin flap may result in rapid remodelling of granulation tissue due to a decrease in expression of the trophic growth factor TGF-beta1 and increased degradation of extracellular matrix due to an alteration in the balance between MMPs and their inhibitor, TIMP-1. Additionally, increased iNOS expression may also favour apoptosis through the generation of free radicals. The additive effect of reduced growth factor expression, increased extracellular matrix turnover, and nitric oxide generation may result in the fibroblast and vascular cell apoptosis seen during the rapid remodelling of this tissue. Animals Apoptosis Female Gene Expression Granulation Tissue/metabolism/pathology Growth Substances/metabolism In Situ Hybridization Metalloendopeptidases/metabolism Nitric Oxide Synthase/metabolism RNA, Messenger/genetics Rats Rats, Wistar Skin Transplantation/pathology Surgical Flaps/pathology Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism Transforming Growth Factor beta/genetics/metabolism Transforming Growth Factor beta1 Dewey 616.07 Dewey 617 137 Département de pathologie et immunologie 21F 57 Département de chirurgie 222 false 72 Groupe Pittet Cuenod Brigitte (chirurgie plastique et reconstructive) 96 Journal of pathology 197 1 b904b5ef-edf9-4a41-a31f-2d0277d9c781 Article (Published version) Restricted 1074_ftp.pdf 1188059 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression	Journal of pathology			2002	552	0

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Desmouliere, Alexis Xavier Marie J.