Krista Morales1, Leahana Rowehl2, Jason Smith1, Rich Cole3, Fang Liu4, Barb Beyer1, Bruce J Herron3. 1. Wadsworth Center , NYS Department of Health, Albany, New York. 2. Forensic Biology, State University of New York at Albany , Albany, New York. 3. Wadsworth Center , NYS Department of Health, Albany, New York. ; School of Public Health, State University of New York at Albany , Albany, New York. 4. School of Public Health, State University of New York at Albany , Albany, New York.
Abstract
Objective: MRL/MpJ mice are known for enhanced healing, but mechanistic details or how specific aspects of wounding (e.g., angiogenesis) contribute to healing are unknown. While previous studies investigated the systemic effects of immunity in MRL/MpJ healing, few have focused on tissue-intrinsic effects. Approach:Ex vivo skin biopsies from MRL/MpJ and C57BL/6J mice were cultured in ex vivo conditions that favor endothelial cell growth to compare their angiogenic potential. We localized enhanced angiogenesis quantitative trait loci (QTL) in an F2 intercross. We then performed an expression analysis in cultured skin biopsies from MRL/MpJ and C57BL/6J mice to determine the pathways that are associated with the capacity for differential growth. Results: MRL/MpJ biopsies have a two- to threefold greater growth potential than C57BL/6J mice, supporting the hypothesis that angiogenesis may contribute to enhanced healing in MRL/MpJ skin. We mapped two QTLs that are unique from previously mapped MRL/MpJ wound healing QTLs and detected interactions between wound healing QTLs and loci in this cross. Additionally, we found that pathways previously implicated in MRL/MpJ healing are also enriched in skin biopsies. Innovation: We have developed a novel approach to determine how specific aspects of tissue development contribute to wound healing that will ultimately lead to the discovery of unidentified genes that contribute to enhanced healing. Conclusion: We have shown that, consistent with previous studies following wound closure in MRL/MpJ mice, vessel growth during healing is also influenced by genetic background. Our ongoing work will identify the genetic factors that should be useful biomarkers or as therapeutic targets for enhanced wound healing.
Objective: MRL/MpJ mice are known for enhanced healing, but mechanistic details or how specific aspects of wounding (e.g., angiogenesis) contribute to healing are unknown. While previous studies investigated the systemic effects of immunity in MRL/MpJ healing, few have focused on tissue-intrinsic effects. Approach:Ex vivo skin biopsies from MRL/MpJ and C57BL/6J mice were cultured in ex vivo conditions that favor endothelial cell growth to compare their angiogenic potential. We localized enhanced angiogenesis quantitative trait loci (QTL) in an F2 intercross. We then performed an expression analysis in cultured skin biopsies from MRL/MpJ and C57BL/6J mice to determine the pathways that are associated with the capacity for differential growth. Results: MRL/MpJ biopsies have a two- to threefold greater growth potential than C57BL/6J mice, supporting the hypothesis that angiogenesis may contribute to enhanced healing in MRL/MpJ skin. We mapped two QTLs that are unique from previously mapped MRL/MpJ wound healing QTLs and detected interactions between wound healing QTLs and loci in this cross. Additionally, we found that pathways previously implicated in MRL/MpJ healing are also enriched in skin biopsies. Innovation: We have developed a novel approach to determine how specific aspects of tissue development contribute to wound healing that will ultimately lead to the discovery of unidentified genes that contribute to enhanced healing. Conclusion: We have shown that, consistent with previous studies following wound closure in MRL/MpJ mice, vessel growth during healing is also influenced by genetic background. Our ongoing work will identify the genetic factors that should be useful biomarkers or as therapeutic targets for enhanced wound healing.
Authors: Thomas A Davis; Mihret Amare; Shruti Naik; Alexander L Kovalchuk; Douglas Tadaki Journal: Wound Repair Regen Date: 2007 Jul-Aug Impact factor: 3.617
Authors: Robert B Chadwick; Liming Bu; Hongrun Yu; Yan Hu; Jon E Wergedal; Subburaman Mohan; David J Baylink Journal: Wound Repair Regen Date: 2007 Mar-Apr Impact factor: 3.617
Authors: Johane Robitaille; Marcia L E MacDonald; Ajamete Kaykas; Laird C Sheldahl; Jutta Zeisler; Marie-Pierre Dubé; Lin-Hua Zhang; Roshni R Singaraja; Duane L Guernsey; Binyou Zheng; Lee F Siebert; Ann Hoskin-Mott; Michael T Trese; Simon N Pimstone; Barkur S Shastry; Randall T Moon; Michael R Hayden; Y Paul Goldberg; Mark E Samuels Journal: Nat Genet Date: 2002-08-12 Impact factor: 38.330
Authors: Dmitri Gourevitch; Lise Clark; Pan Chen; Alexander Seitz; Stefan J Samulewicz; Ellen Heber-Katz Journal: Dev Dyn Date: 2003-02 Impact factor: 3.780
Authors: Dmitri Gourevitch; Andrew V Kossenkov; Yong Zhang; Lise Clark; Celia Chang; Louise C Showe; Ellen Heber-Katz Journal: Adv Wound Care (New Rochelle) Date: 2014-09-01 Impact factor: 4.730