Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts

Cui, Hui Song; Kim, Dong Hyun; Joo, So Young; Cho, Yoon Soo; Kim, June-Bum; Seo, Cheong Hoon

doi:10.1016/j.abb.2022.109215

Cited by 6 publications

(10 citation statements)

References 61 publications

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“…In addition, exosomes derived from different subtypes of stem cells exhibit therapeutic potential and are expected to be an alternative means of developing strategies for curing various diseases [ 43 ]. The profibrotic potency of HTSF-exosomes was demonstrated by promotion of human NF proliferation and differentiation by induction of Smad-dependent and non-Smad-dependent signaling [ 26 ]. HTSF-exosomes contain large amounts of miRNA related to fibrosis, compared with those in NFs [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The profibrotic potency of HTSF-exosomes was demonstrated by promotion of human NF proliferation and differentiation by induction of Smad-dependent and non-Smad-dependent signaling [ 26 ]. HTSF-exosomes contain large amounts of miRNA related to fibrosis, compared with those in NFs [ 26 ]. In addition, exosomes are reported to be involved in the development of organ fibrosis [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…This study was approved by the Hallym University Hangang Sacred Heart Hospital Institutional Review Board (HG 2019-016). Cell culture was performed as previously described [ 26 , 39 ]. Briefly, normal skin and HTS tissues were cut into small pieces, soaked in a Dispase II (1 U/mL; Gibco, Waltham, MA, USA) solution, and maintained at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Exosome extraction was performed as described previously [ 26 ]. The detailed procedure is as follows.…”

Section: Methodsmentioning

confidence: 99%

“…For example, exosomes released by muscle fibroblasts derived from Duchenne muscular dystrophy patients induced an increase in fibrosis markers with α-SMA, collagen, and fibronectin, and activated ERK and Akt signaling in control fibroblasts derived from age-matched subjects [ 25 ]. Recently, we found that exosomes derived from HTS fibroblasts (HTSFs) possess a potent profibrotic property, so we hypothesized that exosomes may play pathological roles in the epidermal development of HTS formation through fibroblast-keratinocyte interaction [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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

Cui

Joo

Lee

et al. 2023

IJMS

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Exosome extraction was performed as described previously [ 26 ]. The detailed procedure is as follows.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cui

Joo

Lee

et al. 2023

IJMS

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Exosomes based strategies for cardiovascular diseases: Opportunities and challenges

Li,

Zhang,

Tan

et al. 2024

Biomaterials

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Heterozygous NF1 dermal fibroblasts modulate exosomal content to promote angiogenesis in a tissue‐engineered skin model of neurofibromatosis type‐1

Roy,

Paquet,

Touzel‐Deschênes

et al. 2023

Journal of Neurochemistry

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Neovascularization is a critical process in tumor progression and malignant transformation associated with neurofibromatosis type 1 (NF1). Indeed, fibroblasts are known to play a key role in the tumoral microenvironment modification by producing an abundant collagenous matrix, but their contribution in paracrine communication pathways is poorly understood. Here, we hypothesized that NF1 heterozygosis in human dermal fibroblasts could promote angiogenesis through exosomes secretion. The purposes of this study are to identify the NF1 fibroblast‐derived exosome protein contents and to determine their proangiogenic activity. Angiogenic proteome measurement confirmed the overexpression of VEGF and other proteins involved in vascularization. Tube formation of microvascular endothelial cells was also enhanced in presence of exosomes derived from NF1 skin fibroblasts. NF1 tissue‐engineered skin (NF1‐TES) generation showed a significantly denser microvessels networks compared to healthy controls. The reduction of exosomes production with an inhibitor treatment demonstrated a drastic decrease in blood vessel formation within the dermis. Our results suggest that NF1 haploinsufficiency alters the dermal fibroblast function and creates a pro‐angiogenic signal via exosomes, which increases the capillary formation. This study highlights the potential of targeting exosome secretion and angiogenesis for therapeutic interventions in NF1.image

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Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts

Cited by 6 publications

References 61 publications

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

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

Exosomes based strategies for cardiovascular diseases: Opportunities and challenges

Heterozygous NF1 dermal fibroblasts modulate exosomal content to promote angiogenesis in a tissue‐engineered skin model of neurofibromatosis type‐1

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