Wnt signaling and the transcription factor Foxn1 contribute to cutaneous wound repair in mice

Abstract

Aim: The transcription factor Foxn1 is a regulator of scar-ended cutaneous wound healing in mice. However, the link between Foxn1 and Wnt signaling has not been explored in the context of cutaneous repair. Here, we investigate the effects of β-catenin-dependent and-independent Wnt signaling represented by Wnt10a and Wnt11, respectively, in healing of full-thickness cutaneous wounds in C57BL/6 mice. Material and Methods: Quantitative polymerase chain reaction, western blot, and immunostaining were performed to assess the spatial and temporal distribution of Wnt10a, Wnt11, and βcatenin in skin during wound healing. A co-culture system consisting of keratinocytes transfected with an adenoviral vector carrying Foxn1-GFP and dermal fibroblasts (DFs) was employed to determine the influence of epidermal signals on the capacity of DFs to produce extracellular matrix (ECM) proteins in vitro. The levels of types I and III collagen in conditioned media from DFs cultures were examined via enzyme-linked immunosorbent assay. Results: The expression of Wnt10a, Wnt11, and β-catenin increased at post-wounding days 14 and 21 when tissue remodeling occurred. Foxn1::Egfp transgenic mice experiments demonstrated that Wnts were abundant in the epidermis adjacent to the wound margin and to a lesser extent in the dermis. The Wnt10a signal colocalized with Foxn1-eGFP in the epithelial tongue and neoepidermis during the initial stage of wound healing. Foxn1 overexpression in keratinocytes affected DFs function related to collagen synthesis. Conclusions: Wnt ligands contribute to cutaneous wound repair, predominantly by engagement in ECM maturation. The data indicates a possible relationship between Foxn1 and Wnts in posttraumatic skin tissue.

Effect of Pig-Adipose-Derived Stem Cells’ Conditioned Media on Skin Wound-Healing Characteristics In Vitro

“…On the contrary, regular cutaneous wound repair involves excessive deposition of extracellular matrix (ECM), mainly collagen type I [ 9 , 10 ], an increase in Tgfβ1 level [ 8 ], and differentiation of dermal fibroblasts (DFs) into myofibroblasts [ 11 ]. Additionally, recent studies on mouse models of wound healing demonstrate that the Wnt pathway contributes to the cellular response to the injury and promotes the development of scar tissue [ 12 , 13 ]. We have previously shown that the expression levels of Wnt10a and Wnt11, the representatives of Wnt/β-catenin-dependent and Wnt/β-catenin-independent pathways, respectively, increase early during the remodeling phase and might contribute to ECM deposition during cutaneous healing in mice [ 13 ].…”

“…Additionally, recent studies on mouse models of wound healing demonstrate that the Wnt pathway contributes to the cellular response to the injury and promotes the development of scar tissue [ 12 , 13 ]. We have previously shown that the expression levels of Wnt10a and Wnt11, the representatives of Wnt/β-catenin-dependent and Wnt/β-catenin-independent pathways, respectively, increase early during the remodeling phase and might contribute to ECM deposition during cutaneous healing in mice [ 13 ].…”

Molekularne mechanizmy działania czynnika transkrypcyjnego FOXN1 w skórze

“…Immunofluorescencyjna detekcja E-kadheryny w pourazowej skórze myszy transgenicznych Foxn1: eGFP. br-brzeg rany, nk-naskórek, sw-skóra właściwa, strzałki wskazują mieszki włosowe, linia przerywana oddziela naskórek od skóry właściwej [63]. Komórki naskórka myszy Foxn1-eGFP wykazywały kolokalizację z WNT11, który jest elementem szlaku zaangażowanego w regulację ekspresji FOXN1 w grasicy.…”

“…Komórki naskórka myszy Foxn1-eGFP wykazywały kolokalizację z WNT11, który jest elementem szlaku zaangażowanego w regulację ekspresji FOXN1 w grasicy. Wskazuje to na udział szlaku WNT w regulacji FOXN1 również w skórze [63].…”

“…Udział FOXN1 w procesie bliznowego gojenia urazów skóry wykazano na modelu myszy transgenicznych, u których jeden allel genu Foxn1 został sprzężony z genem GFP (myszy Foxn1::eGFP) [20,43,53,63]. Model ten umożliwił analizę ekspresji Foxn1 uwidocznioną przez obecność białka GFP w tkance (ryc.…”