ナカニシ トシオ   NAKANISHI Toshio
  中西 敏雄
   所属   医学部 医学科(東京女子医科大学病院)
   職種   特任教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Silibinin Upregulates CXCR4 Expression in Cultured Bone Marrow Cells (BMCs) Especially in Pulmonary Arterial Hypertension Rat Model.
掲載誌名 正式名:Cells
略  称:Cells
ISSNコード:20734409
掲載区分国外
出版社 MDPI
巻・号・頁 9(5),pp.E1276
著者・共著者 ZHANG Tingting†, KAWAGUCHI Nanako*, TSUJI Kunikazu, HAYAMA Emiko, FURUTANI Yoshiyuki, SUGIYAMA Hisashi, NAKANISHI Toshio
担当区分 最終著者
発行年月 2020/05
概要 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% O2). 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.
DOI 10.3390/cells9051276
PMID 32455728