Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice

Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternativ...

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Main Authors: Sheila Jessica Andavania, Mas Rizky Syamsunarno, Agung Putra, Eko Setiawan
Format: Article
Language:English
Published: Cell and BioPharmaceutical Institute 2025-07-01
Series:MCBS (Molecular and Cellular Biomedical Sciences)
Online Access:https://cellbiopharm.com/ojs/index.php/MCBS/article/view/594
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author Sheila Jessica Andavania
Mas Rizky Syamsunarno
Agung Putra
Eko Setiawan
author_facet Sheila Jessica Andavania
Mas Rizky Syamsunarno
Agung Putra
Eko Setiawan
author_sort Sheila Jessica Andavania
collection DOAJ
description Background: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternatives. This study investigated the therapeutic potential of hypoxia-induced mesenchymal stem cell (MSC) exosomes in reducing protein kinase-A (PKA) and VEGFR expression in UVB-induced hyperpigmentation. Materials and methods: A post-test-only control group design was used with 30 male C57BL/6 mice divided into five groups: Healthy group, 0,9% NaCl-treated group, retinol-treated group, and two treatment groups (200 µL Exosomes-treated group and 300 µL Exosomes-treated group. UVB-induced hyperpigmentation was established with 180 mJ/cm² exposures over two weeks. Treatment was administered via subcutaneous injections for seven days. PKA and VEGFR mRNA levels were analyzed using qRT-PCR. Results: PKA expression was significantly lower in the 200 µL Exosomes-treated group (0.34±0.05) and 300 µL Exosomes-treated group (0.21±0.04) groups compared with the 0,9% NaCl-treated group (1.12±0.08) (p<0.001). VEGFR expression similarly decreased in 200 µL Exosomes-treated group (0.32±0.05) and 300 µL Exosomes-treated group (0.18±0.04) versus the 0,9% NaCl-treated group (1.48±0.09) (p<0.001). Both exosome doses achieved reductions comparable to baseline levels observed in the Healthy group. Conclusion: Hypoxia-induced MSC exosomes reduced PKA and VEGFR expression in UVB-induced hyperpigmentation, with the 300 µL dose showing greater efficacy. These findings suggested exosome therapy as a promising alternative for hyperpigmentation treatment.  Keywords: hyperpigmentation, MSC, PKA, VEGFR, melanin
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issn 2527-4384
2527-3442
language English
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spelling doaj-art-439056b8d5814fe59e3be044bcf0a38e2025-08-20T03:29:27ZengCell and BioPharmaceutical InstituteMCBS (Molecular and Cellular Biomedical Sciences)2527-43842527-34422025-07-019291710.21705/mcbs.v9i2.594157Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in MiceSheila Jessica Andavania0Mas Rizky Syamsunarno1Agung Putra2Eko Setiawan3Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, IndonesiaDepartment of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Sumedang, IndonesiaDepartment of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, IndonesiaDepartment of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, IndonesiaBackground: Hyperpigmentation is often exacerbated by ultraviolet-B (UVB) exposure through oxidative stress and activation of pathways like mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor receptor (VEGFR). Current treatments carry risks and necessitate safer alternatives. This study investigated the therapeutic potential of hypoxia-induced mesenchymal stem cell (MSC) exosomes in reducing protein kinase-A (PKA) and VEGFR expression in UVB-induced hyperpigmentation. Materials and methods: A post-test-only control group design was used with 30 male C57BL/6 mice divided into five groups: Healthy group, 0,9% NaCl-treated group, retinol-treated group, and two treatment groups (200 µL Exosomes-treated group and 300 µL Exosomes-treated group. UVB-induced hyperpigmentation was established with 180 mJ/cm² exposures over two weeks. Treatment was administered via subcutaneous injections for seven days. PKA and VEGFR mRNA levels were analyzed using qRT-PCR. Results: PKA expression was significantly lower in the 200 µL Exosomes-treated group (0.34±0.05) and 300 µL Exosomes-treated group (0.21±0.04) groups compared with the 0,9% NaCl-treated group (1.12±0.08) (p<0.001). VEGFR expression similarly decreased in 200 µL Exosomes-treated group (0.32±0.05) and 300 µL Exosomes-treated group (0.18±0.04) versus the 0,9% NaCl-treated group (1.48±0.09) (p<0.001). Both exosome doses achieved reductions comparable to baseline levels observed in the Healthy group. Conclusion: Hypoxia-induced MSC exosomes reduced PKA and VEGFR expression in UVB-induced hyperpigmentation, with the 300 µL dose showing greater efficacy. These findings suggested exosome therapy as a promising alternative for hyperpigmentation treatment.  Keywords: hyperpigmentation, MSC, PKA, VEGFR, melaninhttps://cellbiopharm.com/ojs/index.php/MCBS/article/view/594
spellingShingle Sheila Jessica Andavania
Mas Rizky Syamsunarno
Agung Putra
Eko Setiawan
Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
MCBS (Molecular and Cellular Biomedical Sciences)
title Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
title_full Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
title_fullStr Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
title_full_unstemmed Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
title_short Hypoxia-Induced Mesenchymal Stem Cell Exosomes Modulate Protein Kinase A and VEGFR Expression in Ultraviolet B-Induced Hyperpigmentation in Mice
title_sort hypoxia induced mesenchymal stem cell exosomes modulate protein kinase a and vegfr expression in ultraviolet b induced hyperpigmentation in mice
url https://cellbiopharm.com/ojs/index.php/MCBS/article/view/594
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