miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells
The application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.593638/full |
| _version_ | 1828952232935030784 |
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| author | Yuxin Chen Junfei Huang Zhen Liu Ruosi Chen Danlan Fu Lunan Yang Jin Wang Lijuan Du Lihong Wen Yong Miao Zhiqi Hu |
| author_facet | Yuxin Chen Junfei Huang Zhen Liu Ruosi Chen Danlan Fu Lunan Yang Jin Wang Lijuan Du Lihong Wen Yong Miao Zhiqi Hu |
| author_sort | Yuxin Chen |
| collection | DOAJ |
| description | The application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs regulate HF growth mainly through their unique paracrine properties, raising the possibility of therapies based on extracellular vesicles (EVs). In this study, we explored the effects of EVs from high- and low-passage human scalp follicle dermal papilla cells (DP-EVs) on activation of hair growth, and investigated the underlying mechanism. DP-EVs were isolated by ultracentrifugation and cultured with human scalp follicles, hair matrix cells (MxCs), and outer root sheath cells (ORSCs), and we found low-passage DP-EVs accelerated HF elongation and cell proliferation activation. High-throughput miRNA sequencing and bioinformatics analysis identified 100 miRNAs that were differentially expressed between low- (P3) and high- (P8) passage DP-EVs. GO and KEGG pathway analysis of 1803 overlapping target genes revealed significant enrichment in the BMP/TGF-β signaling pathways. BMP2 was identified as a hub of the overlapping genes. miR-140-5p, which was highly enriched in low-passage DP-EVs, was identified as a potential regulator of BMP2. Direct repression of BMP2 by miR-140-5p was confirmed by dual-luciferase reporter assay. Moreover, overexpression and inhibition of miR-140-5p in DP-EVs suppressed and increased expression of BMP signaling components, respectively, indicating that this miRNA plays a critical role in hair growth and cell proliferation. DP-EVs transport miR-140-5p from DPCs to epithelial cells, where it downregulates BMP2. Therefore, DPC-derived vesicular miR-140-5p represents a therapeutic target for alopecia. |
| first_indexed | 2024-12-14T06:50:31Z |
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| id | doaj.art-2ebaefebd8d445ce9eeb44ba3df25b62 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T06:50:31Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2ebaefebd8d445ce9eeb44ba3df25b622022-12-21T23:12:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-12-01810.3389/fcell.2020.593638593638miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix CellsYuxin ChenJunfei HuangZhen LiuRuosi ChenDanlan FuLunan YangJin WangLijuan DuLihong WenYong MiaoZhiqi HuThe application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs regulate HF growth mainly through their unique paracrine properties, raising the possibility of therapies based on extracellular vesicles (EVs). In this study, we explored the effects of EVs from high- and low-passage human scalp follicle dermal papilla cells (DP-EVs) on activation of hair growth, and investigated the underlying mechanism. DP-EVs were isolated by ultracentrifugation and cultured with human scalp follicles, hair matrix cells (MxCs), and outer root sheath cells (ORSCs), and we found low-passage DP-EVs accelerated HF elongation and cell proliferation activation. High-throughput miRNA sequencing and bioinformatics analysis identified 100 miRNAs that were differentially expressed between low- (P3) and high- (P8) passage DP-EVs. GO and KEGG pathway analysis of 1803 overlapping target genes revealed significant enrichment in the BMP/TGF-β signaling pathways. BMP2 was identified as a hub of the overlapping genes. miR-140-5p, which was highly enriched in low-passage DP-EVs, was identified as a potential regulator of BMP2. Direct repression of BMP2 by miR-140-5p was confirmed by dual-luciferase reporter assay. Moreover, overexpression and inhibition of miR-140-5p in DP-EVs suppressed and increased expression of BMP signaling components, respectively, indicating that this miRNA plays a critical role in hair growth and cell proliferation. DP-EVs transport miR-140-5p from DPCs to epithelial cells, where it downregulates BMP2. Therefore, DPC-derived vesicular miR-140-5p represents a therapeutic target for alopecia.https://www.frontiersin.org/articles/10.3389/fcell.2020.593638/fullextracellular vesicleshair growthdermal papilla cellsmicroRNABMP signaling |
| spellingShingle | Yuxin Chen Junfei Huang Zhen Liu Ruosi Chen Danlan Fu Lunan Yang Jin Wang Lijuan Du Lihong Wen Yong Miao Zhiqi Hu miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells Frontiers in Cell and Developmental Biology extracellular vesicles hair growth dermal papilla cells microRNA BMP signaling |
| title | miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells |
| title_full | miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells |
| title_fullStr | miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells |
| title_full_unstemmed | miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells |
| title_short | miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells |
| title_sort | mir 140 5p in small extracellular vesicles from human papilla cells stimulates hair growth by promoting proliferation of outer root sheath and hair matrix cells |
| topic | extracellular vesicles hair growth dermal papilla cells microRNA BMP signaling |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.593638/full |
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