Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence

Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used <i>in vitro</i> model for studying premature aging. Due to their rich composition of bioactive molecules tha...

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Main Authors: Mirjana Nacka-Aleksić, Andrea Pirković, Aleksandra Vilotić, Maja Kosanović, Dragana Dekanski, Janko Legner, Milica Jovanović Krivokuća
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/6/918
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author Mirjana Nacka-Aleksić
Andrea Pirković
Aleksandra Vilotić
Maja Kosanović
Dragana Dekanski
Janko Legner
Milica Jovanović Krivokuća
author_facet Mirjana Nacka-Aleksić
Andrea Pirković
Aleksandra Vilotić
Maja Kosanović
Dragana Dekanski
Janko Legner
Milica Jovanović Krivokuća
author_sort Mirjana Nacka-Aleksić
collection DOAJ
description Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used <i>in vitro</i> model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular aging and rejuvenation, placental derivatives have a well-established history in anti-aging skincare and therapy. However, trophoblast-derived extracellular vesicle (TEV) effects on D-galactose-induced premature aging in keratinocytes have not been investigated yet. TEV pretreatment for 24 h enhanced cellular resilience against D-galactose-induced stress, judging by the downregulated expression of senescence- and stress-associated markers (p19 and p21, HIF-1α, mTOR), and reduced production of reactive oxygen species and DNA damage. Additionally, TEV pretreatment enhanced keratinocyte proliferation and integrin-β1 subunit expression upon D-galactose exposure, most likely contributing to more efficient wound closure. In conclusion, this study underscores the potential of TEVs to modify expression of stress- and senescence-related proteins in keratinocytes and improve their wound healing properties. Their regenerative and protective characteristics position TEVs as promising candidates for developing innovative procedures to address skin conditions related to premature aging.
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spelling doaj-art-be2b5fc8af6e46a68e169b6ffe043a1c2025-08-20T03:16:18ZengMDPI AGLife2075-17292025-06-0115691810.3390/life15060918Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and SenescenceMirjana Nacka-Aleksić0Andrea Pirković1Aleksandra Vilotić2Maja Kosanović3Dragana Dekanski4Janko Legner5Milica Jovanović Krivokuća6University of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Immunology and Immunoparasitology, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaUniversity of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, SerbiaKeratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used <i>in vitro</i> model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular aging and rejuvenation, placental derivatives have a well-established history in anti-aging skincare and therapy. However, trophoblast-derived extracellular vesicle (TEV) effects on D-galactose-induced premature aging in keratinocytes have not been investigated yet. TEV pretreatment for 24 h enhanced cellular resilience against D-galactose-induced stress, judging by the downregulated expression of senescence- and stress-associated markers (p19 and p21, HIF-1α, mTOR), and reduced production of reactive oxygen species and DNA damage. Additionally, TEV pretreatment enhanced keratinocyte proliferation and integrin-β1 subunit expression upon D-galactose exposure, most likely contributing to more efficient wound closure. In conclusion, this study underscores the potential of TEVs to modify expression of stress- and senescence-related proteins in keratinocytes and improve their wound healing properties. Their regenerative and protective characteristics position TEVs as promising candidates for developing innovative procedures to address skin conditions related to premature aging.https://www.mdpi.com/2075-1729/15/6/918skinagingplacentawound healingregenerative medicine
spellingShingle Mirjana Nacka-Aleksić
Andrea Pirković
Aleksandra Vilotić
Maja Kosanović
Dragana Dekanski
Janko Legner
Milica Jovanović Krivokuća
Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
Life
skin
aging
placenta
wound healing
regenerative medicine
title Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
title_full Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
title_fullStr Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
title_full_unstemmed Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
title_short Trophoblast Extracellular Vesicles as Modulators of Keratinocyte Stress Response and Senescence
title_sort trophoblast extracellular vesicles as modulators of keratinocyte stress response and senescence
topic skin
aging
placenta
wound healing
regenerative medicine
url https://www.mdpi.com/2075-1729/15/6/918
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