Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels
Abstract Background Renal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-d...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-03071-z |
| _version_ | 1811222382552023040 |
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| author | Zhenhua Qiu Zhihui Zhong Yuehan Zhang Haoling Tan Bo Deng Guohuang Meng |
| author_facet | Zhenhua Qiu Zhihui Zhong Yuehan Zhang Haoling Tan Bo Deng Guohuang Meng |
| author_sort | Zhenhua Qiu |
| collection | DOAJ |
| description | Abstract Background Renal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-β1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. Method HK-2, a human RTEC line, was co-treated with TGF-β1 and hucMSC-derived exosomes. Additionally, TGF-β1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. Results TGF-β1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1β, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-β1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-β1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3′-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-β1 induction. Conclusions HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-β1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis. |
| first_indexed | 2024-04-12T08:14:50Z |
| format | Article |
| id | doaj.art-c7741bdc942a4900be17b8cb798a0c44 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-12T08:14:50Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-c7741bdc942a4900be17b8cb798a0c442022-12-22T03:40:50ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111510.1186/s13287-022-03071-zHuman umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levelsZhenhua Qiu0Zhihui Zhong1Yuehan Zhang2Haoling Tan3Bo Deng4Guohuang Meng5Department of Laboratory Medicine, The People’s Hospital of GaozhouDepartment of Laboratory Medicine, The People’s Hospital of GaozhouDepartment of Laboratory Medicine, The People’s Hospital of GaozhouDepartment of Laboratory Medicine, The People’s Hospital of GaozhouDepartment of Laboratory Medicine, The People’s Hospital of GaozhouDepartment of Laboratory Medicine, The People’s Hospital of GaozhouAbstract Background Renal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-β1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. Method HK-2, a human RTEC line, was co-treated with TGF-β1 and hucMSC-derived exosomes. Additionally, TGF-β1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. Results TGF-β1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1β, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-β1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-β1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3′-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-β1 induction. Conclusions HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-β1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.https://doi.org/10.1186/s13287-022-03071-zChronic kidney diseaseExosomemiRNARenal fibrosis |
| spellingShingle | Zhenhua Qiu Zhihui Zhong Yuehan Zhang Haoling Tan Bo Deng Guohuang Meng Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels Stem Cell Research & Therapy Chronic kidney disease Exosome miRNA Renal fibrosis |
| title | Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels |
| title_full | Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels |
| title_fullStr | Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels |
| title_full_unstemmed | Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels |
| title_short | Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels |
| title_sort | human umbilical cord mesenchymal stem cell derived exosomal mir 335 5p attenuates the inflammation and tubular epithelial myofibroblast transdifferentiation of renal tubular epithelial cells by reducing adam19 protein levels |
| topic | Chronic kidney disease Exosome miRNA Renal fibrosis |
| url | https://doi.org/10.1186/s13287-022-03071-z |
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