Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression
The angiogenic potential of mesenchymal stem cells (MSCs) is critical for adult vascular regeneration and repair, which is regulated by various growth factors and cytokines. In the current study, we report that knockdown SUMO-specific peptidase 1 (SENP1) stimulated the SUMOylation of MRTF-A and prev...
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MDPI AG
2023-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/914 |
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| author | Rui Zhang Qingxi Liu Cuicui Lyu Xing Gao Wenjian Ma |
| author_facet | Rui Zhang Qingxi Liu Cuicui Lyu Xing Gao Wenjian Ma |
| author_sort | Rui Zhang |
| collection | DOAJ |
| description | The angiogenic potential of mesenchymal stem cells (MSCs) is critical for adult vascular regeneration and repair, which is regulated by various growth factors and cytokines. In the current study, we report that knockdown SUMO-specific peptidase 1 (SENP1) stimulated the SUMOylation of MRTF-A and prevented its translocation into the nucleus, leading to downregulation of the cytokine and angiogenic factor CCN1, which significantly impacted MSC-mediated angiogenesis and cell migration. Further studies showed that <i>SENP1</i> knockdown also suppressed the expression of a chemokine receptor CXCR4, and overexpression of CXCR4 could partially abrogate MRTF-A SUMOylation and reestablish the CCN1 level. Mutation analysis confirmed that SUMOylation occurred on three lysine residues (Lys-499, Lys-576, and Lys-624) of MRTF-A. In addition, <i>SENP1</i> knockdown abolished the synergistic co-activation of CCN1 between MRTF-A and histone acetyltransferase p300 by suppressing acetylation on histone3K9, histone3K14, and histone4. These results revealed an important signaling pathway to regulate MSC differentiation and angiogenesis by MRTF-A SUMOylation involving cytokine/chemokine activities mediated by CCN1 and CXCR4, which may potentially impact a variety of cellular processes such as revascularization, wound healing, and progression of cancer. |
| first_indexed | 2024-03-11T06:54:03Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:03Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-ed00a8fea40b454ab22a9593eb920c2b2023-11-17T09:47:28ZengMDPI AGBiomedicines2227-90592023-03-0111391410.3390/biomedicines11030914Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 ExpressionRui Zhang0Qingxi Liu1Cuicui Lyu2Xing Gao3Wenjian Ma4Department of Hematology, Tianjin First Central Hospital, Nankai University, Tianjin 300192, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaDepartment of Hematology, Tianjin First Central Hospital, Nankai University, Tianjin 300192, ChinaDepartment of Chemical and Biological Engineering, Qilu Institute of Technology, Jinan 250200, ChinaDepartment of Chemical and Biological Engineering, Qilu Institute of Technology, Jinan 250200, ChinaThe angiogenic potential of mesenchymal stem cells (MSCs) is critical for adult vascular regeneration and repair, which is regulated by various growth factors and cytokines. In the current study, we report that knockdown SUMO-specific peptidase 1 (SENP1) stimulated the SUMOylation of MRTF-A and prevented its translocation into the nucleus, leading to downregulation of the cytokine and angiogenic factor CCN1, which significantly impacted MSC-mediated angiogenesis and cell migration. Further studies showed that <i>SENP1</i> knockdown also suppressed the expression of a chemokine receptor CXCR4, and overexpression of CXCR4 could partially abrogate MRTF-A SUMOylation and reestablish the CCN1 level. Mutation analysis confirmed that SUMOylation occurred on three lysine residues (Lys-499, Lys-576, and Lys-624) of MRTF-A. In addition, <i>SENP1</i> knockdown abolished the synergistic co-activation of CCN1 between MRTF-A and histone acetyltransferase p300 by suppressing acetylation on histone3K9, histone3K14, and histone4. These results revealed an important signaling pathway to regulate MSC differentiation and angiogenesis by MRTF-A SUMOylation involving cytokine/chemokine activities mediated by CCN1 and CXCR4, which may potentially impact a variety of cellular processes such as revascularization, wound healing, and progression of cancer.https://www.mdpi.com/2227-9059/11/3/914human mesenchymal stem cells (hMSCs)SENP1CXCR4CCN1SUMOylationMRTF-A |
| spellingShingle | Rui Zhang Qingxi Liu Cuicui Lyu Xing Gao Wenjian Ma Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression Biomedicines human mesenchymal stem cells (hMSCs) SENP1 CXCR4 CCN1 SUMOylation MRTF-A |
| title | Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression |
| title_full | Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression |
| title_fullStr | Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression |
| title_full_unstemmed | Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression |
| title_short | Knockdown <i>SENP1</i> Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression |
| title_sort | knockdown i senp1 i suppressed the angiogenic potential of mesenchymal stem cells by impacting cxcr4 regulated mrtf a sumoylation and ccn1 expression |
| topic | human mesenchymal stem cells (hMSCs) SENP1 CXCR4 CCN1 SUMOylation MRTF-A |
| url | https://www.mdpi.com/2227-9059/11/3/914 |
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