Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model
Previously we reported that silibinin ameliorated pulmonary arterial hypertension (PAH) in rat PAH models, possibly through the suppression of the CXCR4/SDF-1, until the point where PAH became a severe and irreversible condition. To further investigate how silibinin ameliorates PAH, we first attempt...
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MDPI AG
2020-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1276 |
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| author | Tingting Zhang Nanako Kawaguchi Kunikazu Tsuji Emiko Hayama Yoshiyuki Furutani Hisashi Sugiyama Toshio Nakanishi |
| author_facet | Tingting Zhang Nanako Kawaguchi Kunikazu Tsuji Emiko Hayama Yoshiyuki Furutani Hisashi Sugiyama Toshio Nakanishi |
| author_sort | Tingting Zhang |
| collection | DOAJ |
| description | Previously we reported that silibinin ameliorated pulmonary arterial hypertension (PAH) in rat PAH models, possibly through the suppression of the CXCR4/SDF-1, until the point where PAH became a severe and irreversible condition. To further investigate how silibinin ameliorates PAH, we first attempted to clarify its effect on bone marrow cells (BMCs), since the CXCR4/SDF-1 axis is known to regulate stem cell migration and attachment in BM niches. Rat PAH models were established through a combination of a single subcutaneous injection of monocrotaline (MCT) and chronic hypoxic conditions (10% O<sub>2</sub>). BMCs were harvested and cultured, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry (FCM) were performed to investigate whether silibinin affected CXCR4 expression. Silibinin upregulated the gene expression of stem cell related markers CXCR4, SDF-1, SCF, and c-Kit, inflammatory markers IL-6 and TNFα, mesenchymal stem cell (MSC)-related markers CD44 and CD29, and the granulocyte/monocyte-macrophage marker CD14 in cultured BM in PAH rats, but not in normal rats, except CXCR4. FCM showed that silibinin increased the CXCR4-positive cell population in a granulocyte fraction of cultured BMCs. However, immunohistochemical (IHC) staining showed no significant change in CXCR4 expression in the BM of the tibias. These results suggest that silibinin increases the expression of CXCR4 in BM, and the increased CXCR4-positive cells could be granulocytes/monocyte-macrophages. |
| first_indexed | 2024-03-10T19:41:07Z |
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| id | doaj.art-eaacb732253541fcba16c2310c0e42ae |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T19:41:07Z |
| publishDate | 2020-05-01 |
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| series | Cells |
| spelling | doaj.art-eaacb732253541fcba16c2310c0e42ae2023-11-20T01:17:13ZengMDPI AGCells2073-44092020-05-0195127610.3390/cells9051276Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat ModelTingting Zhang0Nanako Kawaguchi1Kunikazu Tsuji2Emiko Hayama3Yoshiyuki Furutani4Hisashi Sugiyama5Toshio Nakanishi6Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanPediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanDepartment of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo 113-8510, JapanPediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanPediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanPediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanPediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, JapanPreviously we reported that silibinin ameliorated pulmonary arterial hypertension (PAH) in rat PAH models, possibly through the suppression of the CXCR4/SDF-1, until the point where PAH became a severe and irreversible condition. To further investigate how silibinin ameliorates PAH, we first attempted to clarify its effect on bone marrow cells (BMCs), since the CXCR4/SDF-1 axis is known to regulate stem cell migration and attachment in BM niches. Rat PAH models were established through a combination of a single subcutaneous injection of monocrotaline (MCT) and chronic hypoxic conditions (10% O<sub>2</sub>). BMCs were harvested and cultured, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry (FCM) were performed to investigate whether silibinin affected CXCR4 expression. Silibinin upregulated the gene expression of stem cell related markers CXCR4, SDF-1, SCF, and c-Kit, inflammatory markers IL-6 and TNFα, mesenchymal stem cell (MSC)-related markers CD44 and CD29, and the granulocyte/monocyte-macrophage marker CD14 in cultured BM in PAH rats, but not in normal rats, except CXCR4. FCM showed that silibinin increased the CXCR4-positive cell population in a granulocyte fraction of cultured BMCs. However, immunohistochemical (IHC) staining showed no significant change in CXCR4 expression in the BM of the tibias. These results suggest that silibinin increases the expression of CXCR4 in BM, and the increased CXCR4-positive cells could be granulocytes/monocyte-macrophages.https://www.mdpi.com/2073-4409/9/5/1276pulmonary arterial hypertensionsilibininCXCR4bone marrowgranulocytemonocyte-macrophage |
| spellingShingle | Tingting Zhang Nanako Kawaguchi Kunikazu Tsuji Emiko Hayama Yoshiyuki Furutani Hisashi Sugiyama Toshio Nakanishi Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model Cells pulmonary arterial hypertension silibinin CXCR4 bone marrow granulocyte monocyte-macrophage |
| title | Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model |
| title_full | Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model |
| title_fullStr | Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model |
| title_full_unstemmed | Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model |
| title_short | Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model |
| title_sort | silibinin upregulates cxcr4 expression in cultured bone marrow cells bmcs especially in pulmonary arterial hypertension rat model |
| topic | pulmonary arterial hypertension silibinin CXCR4 bone marrow granulocyte monocyte-macrophage |
| url | https://www.mdpi.com/2073-4409/9/5/1276 |
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