LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells
Abstract Background Mesenchymal stem cells (MSCs) exhibit two bidirectional immunomodulatory abilities: proinflammatory and anti-inflammatory regulatory effects. Long noncoding RNAs (lncRNAs) have important functions in the immune system. Previously, we performed high-throughput sequencing comparing...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-022-00858-3 |
| _version_ | 1811265126733447168 |
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| author | Jiajie Lin Zhongyu Xie Zhaoqiang Zhang Ming Li Guiwen Ye Wenhui Yu Jinteng Li Feng Ye Zepeng Su Yunshu Che Peitao Xu Chenying Zeng Peng Wang Yanfeng Wu Huiyong Shen |
| author_facet | Jiajie Lin Zhongyu Xie Zhaoqiang Zhang Ming Li Guiwen Ye Wenhui Yu Jinteng Li Feng Ye Zepeng Su Yunshu Che Peitao Xu Chenying Zeng Peng Wang Yanfeng Wu Huiyong Shen |
| author_sort | Jiajie Lin |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stem cells (MSCs) exhibit two bidirectional immunomodulatory abilities: proinflammatory and anti-inflammatory regulatory effects. Long noncoding RNAs (lncRNAs) have important functions in the immune system. Previously, we performed high-throughput sequencing comparing lncRNA expression profiles between MSCs cocultured with or without CD14+ monocytes and screened out a new lncRNA termed lncRNA MCP1 regulatory factor (MRF). However, the mechanism of MRF in MSCs is still unknown. Methods MRF expression was quantified via qRT–PCR. RNA interference and lentiviruses were used to regulate MRF expression. The immunomodulatory effects of MSCs on monocytes were evaluated via monocyte migration and macrophage polarization assays. RNA pull-down and mass spectrometry were utilized to identify downstream factors of MRF. A dual-luciferase reporter assay was applied to analyze the transcription factors regulating MRF. qRT–PCR, western blotting and ELISAs were used to assess MCP1 expression. A human monocyte adoptive transfer mouse model was applied to verify the function of MRF in vivo. Results MRF was upregulated in MSCs during coculture with CD14+ monocytes. MRF increased monocyte recruitment by upregulating the expression of monocyte chemotactic protein (MCP1). Knockdown of MRF enhanced the regulatory effect of MSCs on restraining M1 polarization and facilitating M2 polarization. Mechanistically, MRF bound to the downstream protein heterogeneous nuclear ribonucleoprotein D (HNRNPD) to upregulate MCP1 expression, and the transcription factor interferon regulatory factor 1 (IRF1) activated MRF transcription early during coculture. The human monocyte adoptive transfer model showed that MRF downregulation in MSCs inhibited monocyte chemotaxis and enhanced the effects of MSCs to inhibit M1 macrophage polarization and promote M2 polarization in vivo. Conclusion We identified the new lncRNA MRF, which exhibits proinflammatory characteristics. MRF regulates the ability of MSCs to accelerate monocyte recruitment and modulate macrophage polarization through the HNRNPD-MCP1 axis and initiates the proinflammatory regulatory process in MSCs, suggesting that MRF is a potential target to improve the clinical effect of MSC-based therapy or correct MSC-related immunomodulatory dysfunction under pathological conditions. |
| first_indexed | 2024-04-12T20:17:13Z |
| format | Article |
| id | doaj.art-6b3c7fa120244a0e9ac10efd029dfcb1 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-04-12T20:17:13Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-6b3c7fa120244a0e9ac10efd029dfcb12022-12-22T03:18:05ZengBMCJournal of Biomedical Science1423-01272022-09-0129111910.1186/s12929-022-00858-3LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cellsJiajie Lin0Zhongyu Xie1Zhaoqiang Zhang2Ming Li3Guiwen Ye4Wenhui Yu5Jinteng Li6Feng Ye7Zepeng Su8Yunshu Che9Peitao Xu10Chenying Zeng11Peng Wang12Yanfeng Wu13Huiyong Shen14Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityCenter for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityCenter for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background Mesenchymal stem cells (MSCs) exhibit two bidirectional immunomodulatory abilities: proinflammatory and anti-inflammatory regulatory effects. Long noncoding RNAs (lncRNAs) have important functions in the immune system. Previously, we performed high-throughput sequencing comparing lncRNA expression profiles between MSCs cocultured with or without CD14+ monocytes and screened out a new lncRNA termed lncRNA MCP1 regulatory factor (MRF). However, the mechanism of MRF in MSCs is still unknown. Methods MRF expression was quantified via qRT–PCR. RNA interference and lentiviruses were used to regulate MRF expression. The immunomodulatory effects of MSCs on monocytes were evaluated via monocyte migration and macrophage polarization assays. RNA pull-down and mass spectrometry were utilized to identify downstream factors of MRF. A dual-luciferase reporter assay was applied to analyze the transcription factors regulating MRF. qRT–PCR, western blotting and ELISAs were used to assess MCP1 expression. A human monocyte adoptive transfer mouse model was applied to verify the function of MRF in vivo. Results MRF was upregulated in MSCs during coculture with CD14+ monocytes. MRF increased monocyte recruitment by upregulating the expression of monocyte chemotactic protein (MCP1). Knockdown of MRF enhanced the regulatory effect of MSCs on restraining M1 polarization and facilitating M2 polarization. Mechanistically, MRF bound to the downstream protein heterogeneous nuclear ribonucleoprotein D (HNRNPD) to upregulate MCP1 expression, and the transcription factor interferon regulatory factor 1 (IRF1) activated MRF transcription early during coculture. The human monocyte adoptive transfer model showed that MRF downregulation in MSCs inhibited monocyte chemotaxis and enhanced the effects of MSCs to inhibit M1 macrophage polarization and promote M2 polarization in vivo. Conclusion We identified the new lncRNA MRF, which exhibits proinflammatory characteristics. MRF regulates the ability of MSCs to accelerate monocyte recruitment and modulate macrophage polarization through the HNRNPD-MCP1 axis and initiates the proinflammatory regulatory process in MSCs, suggesting that MRF is a potential target to improve the clinical effect of MSC-based therapy or correct MSC-related immunomodulatory dysfunction under pathological conditions.https://doi.org/10.1186/s12929-022-00858-3Long noncoding RNAsMesenchymal stem cellsImmunomodulationMRFMCP1 |
| spellingShingle | Jiajie Lin Zhongyu Xie Zhaoqiang Zhang Ming Li Guiwen Ye Wenhui Yu Jinteng Li Feng Ye Zepeng Su Yunshu Che Peitao Xu Chenying Zeng Peng Wang Yanfeng Wu Huiyong Shen LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells Journal of Biomedical Science Long noncoding RNAs Mesenchymal stem cells Immunomodulation MRF MCP1 |
| title | LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells |
| title_full | LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells |
| title_fullStr | LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells |
| title_full_unstemmed | LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells |
| title_short | LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells |
| title_sort | lncrna mrf drives the regulatory function on monocyte recruitment and polarization through hnrnpd mcp1 axis in mesenchymal stem cells |
| topic | Long noncoding RNAs Mesenchymal stem cells Immunomodulation MRF MCP1 |
| url | https://doi.org/10.1186/s12929-022-00858-3 |
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