FOXN1 Transcription Factor in Epithelial Growth and Wound Healing

Abstract

FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pigmented keratinocytes, including nevi, and FOXN1 is an attribute of benign epithelial tumors. The lack of FOXN1 favors the skin regeneration process displayed by nude mice, pointing to FOXN1 as a switch between regeneration and reparative processes. The stem cell niche provides a functional source of cells after the loss of tissue following wounding. The involvement of prodifferentiation factors in the regulation of this pool of stem cells is suggested. However, the exact mechanism is still under question, and we speculate that the FOXN1 transcription factor is involved in this process. This review analyzes the pleiotropic effects of FOXN1 in the skin, its function in the tumorigenesis process, and its potential role in depletion of the stem cell niche after injury, as well as its suggested mechanistic role, acting in a cell-autonomous and a non-cell-autonomous manner during skin self-renewal.

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

“…[12][13][14] For example, FOXN1 is an attribute of benign epithelial tumors. 15 FOXN4 is a tumor suppressor in breast cancer through inhibition of slug. 16 Importantly, FOXN4 is a key regulator in a variety of biological processes during development.…”

RNU (Foxn1RNU-Nude) Rats Demonstrate an Improved Ability to Regenerate Muscle in a Volumetric Muscle Injury Compared to Sprague Dawley Rats

“…While forkhead box proteins ( Fox ) are well studied, the relationship between Foxn1 -deficiency in nude rodents and improved regeneration is not well understood. Foxn1 is a transcription factor that is predominantly expressed in skin cells, and it is hypothesized that Foxn1 regulates the switch between scar-forming and scar-free healing [ 26 ]. In mammals, the scar-forming process occurs in three overlapping phases during wound—inflammation, new tissue formation, remodeling—and these same phases apply to skeletal muscle.…”

“…As stated, RNU animals are often used to prevent immune rejection and reports indicate that T-cell deficiency in these animals suppresses inflammation in skin wounds, suggesting that muscle may also be affected. Furthermore, T-cell deficient animals expressed a different composition of macrophage subtypes, which could contribute to altered regeneration [ 10 , 26 ]. In this study, we hypothesized that repair of a VML defect with an allogeneic DMM would improve histologic and functional evidence of muscle regeneration in RNU rats when compared to immunocompetent Sprague Dawley rats.…”

Development of the Nude Rabbit Model

“…The nude mouse (NuMouse) as an experimental animal model has been well established and applied in diverse biomedical research fields, including immunology, cancer research, stem cell therapy, and skin regeneration ( Zhang et al., 2012 ). The nude phenotype is caused by mutation of the FOXN1 gene, which plays a pivotal role in the differentiation of thymic and skin epithelial cells ( Brissette et al., 1996 ; Grabowska and Wilanowski, 2017 ; Lee et al., 1999 ; Meier et al., 1999 ; Nowell et al., 2011 ; Zuklys et al., 2016 ). In human patients, loss-of-function mutations in the FOXN1 gene lead to a well-described phenotype of nude combined immunodeficiency, which includes congenital alopecia, nail dystrophy, and T cell immunodeficiency ( Palamaro et al., 2014 ; Rota and Dhalla, 2017 ).…”