Wound Healing in Tenascin-X Deficient Mice Suggests that Tenascin-X is Involved in Matrix Maturation Rather than Matrix Deposition

Abstract

Tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence in humans leads to a recessive form of Ehlers-Danlos Syndrome (EDS). TNX deficient patients have hypermobile joints and fragile skin, but unlike the classical type of EDS, no atrophic scars were observed. Anecdotal evidence suggested that wound healing in TNX deficient patients is abnormal, but no detailed study has been performed so far. To address the role of TNX in wound healing, we analyzed skin wound morphology and mechanical properties of scars in TNX knockout (KO) mice. Breaking strength of unwounded skin of KO mice is significantly lower (<50%) than that of wild-type (WT) mice. In the early stage of wound healing when TNX is hardly expressed in WT wounds (day 7), WT and KO skin are of similar strength. After 14 days, when TNX starts to be expressed at moderate levels in wounds of WT mice, the WT scars gain a further increase in breaking strength, whereas KO scars do not progress beyond the mechanical strength of uninjured KO skin. No obvious differences between KO and WT mice were noted in the rate of wound closure, or in expression of fibrillar collagens during wound healing. We conclude that TNX is unlikely to be involved in matrix deposition in the early phase of wound healing, but it is required in the later phase when remodeling and maturation of the matrix establishes and improves its biomechanical properties.

Epigenetics and systemic sclerosis

“…Also, TNXB was shown to be hypomethylated in dcSSc and lcSSc-FB [12]. TNXB encodes a member of the tenascin family of extracellular matrix glycoproteins, which are involved in matrix maturation [14]. These observations indicate that methylation status of the collagen and ECM proteinencoding genes is intimately involved in ECM accumulation in SSc.…”

Tenascin-X: beyond the architectural function

“…49 Interestingly, the genetic background markedly influences EDS manifestations, as the phenotype was less severe on a homogenous (C57BL/6) compared to a mixed (129/SvJ, C57BL/6 and FVB) genetic background. 29,47,49 One possible Indirect immunofluorescence of TN-X performed on cryostat sections of mouse skin after incisional wound (*). TN-X was detected using polyclonal antibodies directed against the bovine TN-X FNIII b9-b10 repeats.…”

“…37 It is also conceivable that TN-X might be involved in elastic fibers formation and maturation. 29,58 Figure 3. Model of TN-X integration within the collagenous network.…”

“…2B). TN-X then becomes re-expressed later during healing, at stages coinciding with matrix assembly and maturation 29 ( Fig. 2B).…”

Tenascins and the Importance of Adhesion Modulation

“…Ehlers-Danlos Syndrome is characterized as hyperextensible skin and joints, susceptibility to bruising, and poor wound healing. The role of tenascin-X in this syndrome, which previously was believed to be limited to collagens and enzymes that Tenascin-X Ehlers-Danlos Syndrome-related phenotypes Abnormal epidermal scars, hyperextensible skin, fragile skin, reduced dermal fibrillar collagen, abnormal fibrillar collagen Mao et al 2002;Minamitani et al 2004aMinamitani et al , 2004bEgging et al 2006Egging et al , 2007 Miscellaneous phenotypes Abnormal vaginal plug location, rectal prolapse Egging et al 2008 Abnormal accumulation of dermal lipids Matsumoto et al 2004 Abnormal melanoma growth and metastasis Matsumoto et al 2002 help modify and assemble collagens, was shown convincingly by the phenotype of the tenascin-X knockout mouse (Table 3) (Mao et al 2002; see also Egging et al 2006). These mice have easily deformable skin and a significant decrease in the number of collagen fibrils in the dermis.…”