Exosome Derived from ADSCs Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Wang, Xiu; Si, Yue; Pang, Jinlong; Líu, Hao; Li, Shanshan; Ding, Qi; Wang, Yushuai

doi:10.1111/php.13370

Cited by 36 publications

(33 citation statements)

References 44 publications

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“…Several studies have found that ADSC transplantation therapy can reverse scleroderma-induced cutaneous brosis [13,14]. Exosome secretion by ADSCs plays an important role in microenvironmental regulation via delivery of bioinformatics molecule [15,16]. The present study found that ADSC exosome treatment avoids dermal thickening and brosis induced by bleomycin administration.…”

Section: Discussionsupporting

confidence: 63%

Exosomes From ADSCs Attenuate Bleomycin-Induced Skin Fibrosis And Oxidative Stress In Scleroderma Via Circ-Zfyve9 Delivery

Zhang

Tang

Zhu

et al. 2021

Preprint

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Background: Systemic sclerosis (SSc) is autoimmune trait affecting several organs, which is identified by thickening of dermis and connective tissue affected by collagen accumulation, as well as vascular injuries inducing hypoxia. Methods: In this investigation, adipose-derived stem cells (ADSCs) were separated from the ADSC exosomes and a bleomycin-induced SSc mouse model was constructed. We employed high-throughput sequencing to study abnormal expression of circular RNAs (circRNAs) in SSc skin tissues with or without ADSC exosome treatment. The regulatory mechanism and targets were studied using bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation experiments, and RT-qPCR detection. Results: ADSC exosome treatment prevented dermal thickening and fibrosis in bleomycin-induced scleroderma. In addition, circ-Zfyve9 was demonstrated to have an important function in ADSC exosome-mediated skin tissue protection. GPX4 and miR-135 were shown to be circ-Zfyve9 downstream targets. Overexpressing miR-135 or downregulating GPX4 reversed circ-Zfyve9 promotion effects rupon angiopoiesis by promoting lipidosome ROS in EPCs under hypoxic conditions. Overexpressing miR-135 or downregulating GPX4 reversed the circ-Zfyve9 inhibition effect on fibrosis in myofibroblasts under hypoxic conditions. Overexpressing circ-Zfyve9 increased the therapeutic effect of ADSC exosomes. Conclusions: Taken together, the present study results show that the exosomes from ADSCs attenuate bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery.

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Section: Discussionsupporting

confidence: 63%

Exosomes From ADSCs Attenuate Bleomycin-Induced Skin Fibrosis And Oxidative Stress In Scleroderma Via Circ-Zfyve9 Delivery

Zhang

Tang

Zhu

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Several studies have found that ADSC transplantation therapy can reverse scleroderma-induced cutaneous brosis [16,17]. Exosome secretion by ADSCs plays an important role in microenvironmental regulation via delivery of bioinformatics molecule [18,19]. The present study found that ADSC exosome treatment avoids dermal thickening and brosis induced by bleomycin administration.…”

Section: Discussionsupporting

confidence: 63%

Exosome s from ADSCs attenuate bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery

Zhang

Tang

Zhu

et al. 2022

Preprint

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Background Systemic sclerosis (SSc) is an autoimmune trait affecting several organs and is identified by thickening of the dermis and connective tissue affected by collagen accumulation, as well as vascular injuries inducing hypoxia. Methods In this investigation, adipose-derived stem cells (ADSCs) and their exosomes were separated, and a bleomycin-induced SSc mouse model was constructed. High-throughput sequencing was employed to study abnormal expression of circular RNAs (circRNAs) in SSc skin tissues with or without ADSC exosome treatment. The regulatory mechanism and targets were studied using bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation experiments, and RT-qPCR detection analysis. Results In this study, exosomes from ADSCs were successfully isolated. In addition, the exosome treatment prevented dermal thickening and fibrosis in bleomycin-induced scleroderma. In addition, circ-Zfyve9 was demonstrated to have an important function in ADSC exosome-mediated skin tissue protection. GPX4 and miR-135 were shown to be circ-Zfyve9 downstream targets. Overexpressing miR-135 or downregulating GPX4 reversed the promotion effects of circ-Zfyve9 to angiopoiesis by increasing lipidosome ROS in EPCs under hypoxic conditions. Overexpressing miR-135 or downregulating GPX4 reversed the inhibition effect of circ-Zfyve9 on fibrosis in myofibroblasts under hypoxic conditions. Overexpressing circ-Zfyve9 increased the therapeutic effect of ADSC exosomes. Conclusions Taken together, the present study results show that the exosomes from ADSCs attenuate bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery.

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“…There were recently reported studies elucidating that human umbilical cord mesenchymal stem cellderived exosomes (hucMSC-Exo) significantly reduced the expression of collagen and p-Smad2 to alleviate liver fibrosis in vivo [60]. Other than that, MSC-Exo regulated the fibrosis repair of injured endometrium by downregulating Smad signaling pathway, demonstrating that phosphorylation levels of Smad2 were gradually decreased with the increased concentration of exosome in BMSCs and Exo treatment groups [61]. Besides, levels of collagen, α-SMA, and phosphorylation of Smad2/3 were markedly decreased in fibroblasts treated with hucMSC-derived exosomes, suggesting that hucMSC-derived exosomes could inhibit dermal fibroblast-myofibroblast transition by inhibiting the Smad signaling pathway [62].…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis

et al. 2021

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Background Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. Methods ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson’s trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. Results The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. Conclusions This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

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Exosome Derived from ADSCs Attenuates Ultraviolet B‐mediated Photoaging in Human Dermal Fibroblasts

Cited by 36 publications

References 44 publications

Exosomes From ADSCs Attenuate Bleomycin-Induced Skin Fibrosis And Oxidative Stress In Scleroderma Via Circ-Zfyve9 Delivery

Exosomes From ADSCs Attenuate Bleomycin-Induced Skin Fibrosis And Oxidative Stress In Scleroderma Via Circ-Zfyve9 Delivery

Exosome s from ADSCs attenuate bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery

Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis

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