Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-der...

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Main Authors: Hui Song Cui, So Young Joo, Seung Yeol Lee, Yoon Soo Cho, Dong Hyun Kim, Cheong Hoon Seo
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/7/6132
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author Hui Song Cui
So Young Joo
Seung Yeol Lee
Yoon Soo Cho
Dong Hyun Kim
Cheong Hoon Seo
author_facet Hui Song Cui
So Young Joo
Seung Yeol Lee
Yoon Soo Cho
Dong Hyun Kim
Cheong Hoon Seo
author_sort Hui Song Cui
collection DOAJ
description Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.
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spelling doaj.art-f7880a6caeb54899b933150faacd87712023-11-17T16:46:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247613210.3390/ijms24076132Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human SkinHui Song Cui0So Young Joo1Seung Yeol Lee2Yoon Soo Cho3Dong Hyun Kim4Cheong Hoon Seo5Burn Institute, Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of KoreaDepartment of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of KoreaDepartment of Physical Medicine and Rehabilitation, College of Medicine, Soonchunhyang University Hospital, Bucheon 14158, Republic of KoreaDepartment of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of KoreaDepartment of Rehabilitation Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 05355, Republic of KoreaDepartment of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07247, Republic of KoreaEpidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.https://www.mdpi.com/1422-0067/24/7/6132hypertrophic scarfibroblastexosomekeratinocyteproliferationdifferentiation
spellingShingle Hui Song Cui
So Young Joo
Seung Yeol Lee
Yoon Soo Cho
Dong Hyun Kim
Cheong Hoon Seo
Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
International Journal of Molecular Sciences
hypertrophic scar
fibroblast
exosome
keratinocyte
proliferation
differentiation
title Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
title_full Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
title_fullStr Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
title_full_unstemmed Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
title_short Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
title_sort effect of hypertrophic scar fibroblast derived exosomes on keratinocytes of normal human skin
topic hypertrophic scar
fibroblast
exosome
keratinocyte
proliferation
differentiation
url https://www.mdpi.com/1422-0067/24/7/6132
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