title: Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.
abstract: Rationale:The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates.Method:We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout.Conclusion:We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Kristen B
authors.initials: KB
authors.lastname: Long
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Burgwin
authors.affiliation: University Laboratory Animal Resources, Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Richard
authors.initials: R
authors.lastname: Huneke
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Artlett
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Blankenhorn