Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal MicroRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1/TGF-β Signaling Axis

Overview

Journal Clin Cosmet Investig Dermatol

Publisher Dove Medical Press

Specialty Dermatology

Date 2020 Dec 28

PMID 33364805

Citations 31

Authors

Guoxiu Cao

Bei Chen

Xian Zhang

Hongyun Chen

Affiliations

Soon will be listed here.

Abstract

Introduction: Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs-derived exosomes on skin wound healing.

Methods: ADMSCs were extracted and ADMSCs-derived exosomes were identified. Skin damage models were established by treating HaCaT cells and human skin fibroblasts with HO. Next, the roles of ADMSCs and their derived exosomes were investigated. The exosomal miRNA then was analyzed, and the function of miRNA on the HO-induced cells was studied by miRNA suppression. Bioinformatics analysis, luciferase activity and RIP assays were implemented to find the target genes ofthe miRNA and the modulated pathways. A mouse skin damage model was induced to elucidate the effects of exosomes in vivo by injecting exosomes.

Results: HO treatment significantly reduced the viability of HaCaT cells and increased their apoptosis rate. Co-culture with ADMSCs or their derived exosomes could improve the cell damage caused by HO. Meanwhile, HO treatment promoted the internalization of exosomes. ADMSCs and their derived exosomes significantly increased miR-19b expression in the recipient cells, while inhibiting miR-19b resulted in a reduction in the therapeutic effect of ADMSCs-derived exosomes. Besides, miR-19b regulated the TGF-β pathway by targeting CCL1. The therapeutic effect of exosomes was further confirmed by a mouse model of skin damage.

Conclusion: Our study indicates that exosomal miR-19b derived from ADMSCs regulates the TGF-β pathway by targeting CCL1, thereby promoting the healing of skin wounds.

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References

Li Z, Cai J, Cao X . MiR-19 suppresses fibroblast-like synoviocytes cytokine release by targeting toll like receptor 2 in rheumatoid arthritis. Am J Transl Res. 2017; 8(12):5512-5518. PMC: 5209502. View

Cho B, Kim J, Ha D, Yi Y . Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther. 2018; 9(1):187. PMC: 6042362. DOI: 10.1186/s13287-018-0939-5. View

Esposito D, Overall J, Grace M, Komarnytsky S, Lila M . Alaskan Berry Extracts Promote Dermal Wound Repair Through Modulation of Bioenergetics and Integrin Signaling. Front Pharmacol. 2019; 10:1058. PMC: 6776586. DOI: 10.3389/fphar.2019.01058. View

Zhao G, Liu F, Liu Z, Zuo K, Wang B, Zhang Y . MSC-derived exosomes attenuate cell death through suppressing AIF nucleus translocation and enhance cutaneous wound healing. Stem Cell Res Ther. 2020; 11(1):174. PMC: 7212595. DOI: 10.1186/s13287-020-01616-8. View

Sanchez-Sanchez R, Brena-Molina A, Martinez-Lopez V, Melgarejo-Ramirez Y, De Dios L, Gomez-Garcia R . Generation of Two Biological Wound Dressings as a Potential Delivery System of Human Adipose-Derived Mesenchymal Stem Cells. ASAIO J. 2015; 61(6):718-25. PMC: 4632116. DOI: 10.1097/MAT.0000000000000277. View

Long S, Zhao N, Ge L, Wang G, Ran X, Wang J . MiR-21 ameliorates age-associated skin wound healing defects in mice. J Gene Med. 2018; 20(6):e3022. DOI: 10.1002/jgm.3022. View

Duan L, Duan D, Wei W, Sun Z, Xu H, Guo L . MiR-19b-3p attenuates IL-1β induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6. Mol Cell Biochem. 2019; 459(1-2):205-214. DOI: 10.1007/s11010-019-03563-2. View

Zhao Y, Wang Q, Jin Y, Li Y, Nie C, Huang P . Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1, Targeting FGFR2IIIc for Skin Wound Healing. Cell Physiol Biochem. 2018; 49(3):1033-1048. DOI: 10.1159/000493287. View

Valvis S, Waithman J, Wood F, Fear M, Fear V . The Immune Response to Skin Trauma Is Dependent on the Etiology of Injury in a Mouse Model of Burn and Excision. J Invest Dermatol. 2015; 135(8):2119-2128. DOI: 10.1038/jid.2015.123. View

10.

Li Q, Zhao H, Chen W, Huang P, Bi J . Human keratinocyte-derived microvesicle miRNA-21 promotes skin wound healing in diabetic rats through facilitating fibroblast function and angiogenesis. Int J Biochem Cell Biol. 2019; 114:105570. DOI: 10.1016/j.biocel.2019.105570. View

11.

Luo X, Shao J, Xie R, Zeng L, Li X, Qiu S . Micro RNA-19a interferes with IL-10 expression in peripheral dendritic cells of patients with nasal polyposis. Oncotarget. 2017; 8(30):48915-48921. PMC: 5564735. DOI: 10.18632/oncotarget.16555. View

12.

Park H, Park N, Kim S, Jeong K, Lee E, Lee E . Potential Wound Healing Activities of Galla Rhois in Human Fibroblasts and Keratinocytes. Am J Chin Med. 2015; 43(8):1625-36. DOI: 10.1142/S0192415X15500925. View

13.

Roh J, Lee J, Kim E, Shin D . Plasticity of oral mucosal cell sheets for accelerated and scarless skin wound healing. Oral Oncol. 2017; 75:81-88. DOI: 10.1016/j.oraloncology.2017.10.024. View

14.

Li Z, Chan K, Qi Y, Lu L, Ning F, Wu M . Participation of CCL1 in Snail-Positive Fibroblasts in Colorectal Cancer Contribute to 5-Fluorouracil/Paclitaxel Chemoresistance. Cancer Res Treat. 2017; 50(3):894-907. PMC: 6056976. DOI: 10.4143/crt.2017.356. View

15.

He L, Zhu C, Jia J, Hao X, Yu X, Liu X . ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway. Biosci Rep. 2020; 40(5). PMC: 7214401. DOI: 10.1042/BSR20192549. View

16.

Li D, Peng H, Qu L, Sommar P, Wang A, Chu T . miR-19a/b and miR-20a Promote Wound Healing by Regulating the Inflammatory Response of Keratinocytes. J Invest Dermatol. 2020; 141(3):659-671. DOI: 10.1016/j.jid.2020.06.037. View

17.

Wang Z, Zhu X . Exosomal miR-19b-3p communicates tubular epithelial cells and M1 macrophage. Cell Death Dis. 2019; 10(10):762. PMC: 6787089. DOI: 10.1038/s41419-019-2008-0. View

18.

Li M, Cui X, Guan H . MicroRNAs: pivotal regulators in acute myeloid leukemia. Ann Hematol. 2020; 99(3):399-412. DOI: 10.1007/s00277-019-03887-5. View

19.

Long M, Rojo de la Vega M, Wen Q, Bharara M, Jiang T, Zhang R . An Essential Role of NRF2 in Diabetic Wound Healing. Diabetes. 2016; 65(3):780-93. PMC: 4764153. DOI: 10.2337/db15-0564. View

20.

Xu H, Liu X, Ni H . Clinical significance of miR-19b-3p in patients with sepsis and its regulatory role in the LPS-induced inflammatory response. Eur J Med Res. 2020; 25(1):9. PMC: 7079357. DOI: 10.1186/s40001-020-00408-3. View