Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing.

Barbara Gawronska-Kozak,Katarzyna Walendzik,Sylwia Machcinska,Marta Kopcewicz,Joanna Wiśniewska,Artur Padzik

doi:10.3390/ijms23010257

Abstract

Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, the studies concerning its molecular regulation are limited. In the present paper, we ask whether the introduction of two transcription factors, Foxn1 and Hif-1α, into the post-wounded skin of Foxn1−/− mice regulates dWAT during wound healing (days 3 and 6). We have chosen lentivirus vectors (LVs) as a tool to deliver Foxn1 and Hif-1α into the post-wounded skin. We documented that combinations of both transgenes reduces the number, size and diameter of dermal adipocytes at the wound bed area. The qRT-PCR analysis of pro-adipogenic genes, revealed that LV-Hif-1α alone, or combined with LV-Foxn1, increases the mRNA expression of Pparγ, Glut 4 and Fasn at post-wounding day 6. However, the most spectacular stimulatory effect of Foxn1 and/or Hif-1α was observed for Igf2, the growth factor participating in adipogenic signal transduction. Our data also shows that Foxn1/Hif-1α, at post-wounding day 3, reduces levels of CD68 and MIP-1γ mRNA expression and the percentage of CD68 positive cells in the wound site. In conclusion, the present data are the first to document that Foxn1 and Hif-1α cooperatively (1) regulate dWAT during the proliferative phase of skin wound healing through the Igf2 signaling pathway, and (2) reduce the macrophages content in the wound site.

Highlights

The skin, the largest organ of the body, creates the wall between the internal organs and the external environment, thereby forming the first barrier that protects against threats, such as injuries or infections
The results of the present in vivo study can be viewed in terms of three separate aspects of skin biology: (1) the role of Foxn1 and Hif-1α in the regulation of Dermal white adipose tissue (dWAT) in wounded skin through the Igf2 signaling pathway; (2) the control of the macrophages content in post-wounded skin, which is synchronized by Foxn1 and Hif-1α and (3) Lentivirus vectors (LVs)
Delivery as an efficient and valuable method to study the effects of Foxn1 and Hif-1α on skin biology

Summary

Introduction

The skin, the largest organ of the body, creates the wall between the internal organs and the external environment, thereby forming the first barrier that protects against threats, such as injuries or infections. The last 20 years of study have brought profound changes in the view of skin structure complexity and, as a consequence, of its operation and function [1,2,3]. The dermis, the main part of the skin considered as a uniform structure, appears to be built up by at least two layers: the upper papillary layer, adjacent to the epidermis, and the lower reticular layer [1]. Those layers differ, due to dermal fibroblast heterogeneity and density and extracellular matrix (ECM) composition [2,4]. A study by Wolnicka et al revealed that the mouse dermis contains cells that express the adipocyte marker

Methods

Results

Conclusion