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

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<su...

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Main Authors: Barbara Gawronska-Kozak, Katarzyna Walendzik, Sylwia Machcinska, Artur Padzik, Marta Kopcewicz, Joanna Wiśniewska
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/1/257
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author Barbara Gawronska-Kozak
Katarzyna Walendzik
Sylwia Machcinska
Artur Padzik
Marta Kopcewicz
Joanna Wiśniewska
author_facet Barbara Gawronska-Kozak
Katarzyna Walendzik
Sylwia Machcinska
Artur Padzik
Marta Kopcewicz
Joanna Wiśniewska
author_sort Barbara Gawronska-Kozak
collection DOAJ
description 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<sup>−/−</sup> 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 <i>Pparγ</i>, <i>Glut 4</i> and <i>Fasn</i> 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 <i>CD68</i> and <i>MIP-1γ</i> 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.
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spelling doaj.art-baec68f930ad4d96848bd30c815391112023-11-23T11:37:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123125710.3390/ijms23010257Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound HealingBarbara Gawronska-Kozak0Katarzyna Walendzik1Sylwia Machcinska2Artur Padzik3Marta Kopcewicz4Joanna Wiśniewska5Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandVirus Vector Core, Turku Centre for Biotechnology BioCity, 20520 Turku, FinlandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandDermal 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<sup>−/−</sup> 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 <i>Pparγ</i>, <i>Glut 4</i> and <i>Fasn</i> 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 <i>CD68</i> and <i>MIP-1γ</i> 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.https://www.mdpi.com/1422-0067/23/1/257skinwound healingdermal white adipose tissueFoxn1Hif-1α
spellingShingle Barbara Gawronska-Kozak
Katarzyna Walendzik
Sylwia Machcinska
Artur Padzik
Marta Kopcewicz
Joanna Wiśniewska
Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
International Journal of Molecular Sciences
skin
wound healing
dermal white adipose tissue
Foxn1
Hif-1α
title Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
title_full Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
title_fullStr Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
title_full_unstemmed Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
title_short Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
title_sort dermal white adipose tissue dwat is regulated by foxn1 and hif 1α during the early phase of skin wound healing
topic skin
wound healing
dermal white adipose tissue
Foxn1
Hif-1α
url https://www.mdpi.com/1422-0067/23/1/257
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