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Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.

ABSTRACT: BACKGROUND:We have reported that WNT10A plays a critical role in the growth of fibroblasts/myofibroblasts and microvascular endothelial cells, i.e.; wound healing/scarring. To ascertain the in vivo regulatory, central functions of WNT10A, we examined the net effects of WNT10A depletion using WNT10A-deficient mice (WNT10A-/-). METHODS AND RESULTS:We generated WNT10A-/-mice, displaying a range of unique phenotypes of morpho/organogenetic failure, such as growth retardation, alopecia, kyphosis and infertility, and then focused on the functions of WNT10A in wound healing. We subjected C57BL/6J wild-type (WT) or WNT10A-/-mice to skin ulcer formation. The WNT10A-/-mice had significantly larger injured areas and delayed wound healing, which were associated with (a) a smaller number of fibroblasts/myofibroblasts and microvessels; and (b) more reduced expression and synthesis of collagen, compared with WT mice with intact WNT10A expression, especially in those with activated myofibroblasts. CONCLUSIONS:These observations indicate that WNT10A signaling can play a pivotal in vivo role in wound healing by regulating the expression and synthesis of collagen, as one of fibrogenic factors, at least in part, and critical in vivo roles of WNT10A-mediated effective wound healing are extremely closely associated with collagen expression.

SUBMITTER: Wang KY

PROVIDER: S-EPMC5875851 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.

Wang Ke-Yong KY Yamada Sohsuke S Izumi Hiroto H Tsukamoto Manabu M Nakashima Tamiji T Tasaki Takashi T Guo Xin X Uramoto Hidetaka H Sasaguri Yasuyuki Y Kohno Kimitoshi K

PloS one 20180329 3

<h4>Background</h4>We have reported that WNT10A plays a critical role in the growth of fibroblasts/myofibroblasts and microvascular endothelial cells, i.e.; wound healing/scarring. To ascertain the in vivo regulatory, central functions of WNT10A, we examined the net effects of WNT10A depletion using WNT10A-deficient mice (WNT10A-/-).<h4>Methods and results</h4>We generated WNT10A-/-mice, displaying a range of unique phenotypes of morpho/organogenetic failure, such as growth retardation, alopecia ...[more]

PMID: 29596490

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Project description:UnlabelledIn this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF+O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF+O2 dressings improve re-epithelialization (p<0.0001) and synthesis of collagen over controls (p<0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF+O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF+O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology.Statement of significanceThis work presents the first application of a novel class of oxygen delivering biomaterials (methacrylamide chitosan modified with perfluorocarbon chains (MACF)) as a hydrogel wound dressing. This manuscript also contains strong focus on the biochemical benefits of MACF dressings on underlying mechanisms vital to successful wound healing. In this vein, this manuscript presents the application of applied metabolomics (tandem mass spectroscopy) to uncover biomaterial interactions with wound healing mechanisms. We believe the approaches described in this manuscript will be of great interest to biomedical scientists and particularly to researchers studying wound healing, metabolomics, applied biomaterials and regenerative medicine.

Dataset Information

Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.

Publications

Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.

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