Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway
Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway
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淫羊藿苷通过靶向MAPK通路保护再生障碍性贫血骨髓间充质干细胞
DOI：
10.1007/s11033-022-07645-1
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发表时间：
2022-06-16
影响因子：
2.8
通讯作者：
Shen, Jianping
中科院分区：
文献类型：
--
作者：
Deng, Shu;Zeng, Yuqing;Shen, Jianping
研究背景淫羊藿苷是从淫羊藿中提取的主要药理活性黄酮类化合物，在多种疾病中具有调节细胞过程的作用。本研究旨在探讨淫羊藿苷对再生障碍性贫血（AA）骨髓间充质干细胞（BMSCs）增殖和成脂的影响及其机制。方法和结果从苯和环磷酰胺诱导的AA大鼠胫骨和股骨后部分离骨髓间充质干细胞，并用淫羊藿苷灌胃。分离的骨髓基质细胞进行形态学和免疫学鉴定，阳性标志物（CD 29和CD 90）和阴性标志物（CD 34和CD 45）。CCK-8法检测BMSCs增殖情况。流式细胞仪检测细胞凋亡和细胞周期。油红O染色观察成脂情况。通过qRT-PCR测量PPAR γ、C/EBP-α和FABP 4的mRNA表达。采用Western blotting检测p-p38/p38、p-JNK/JNK、p-ERK/ERK、PPAR γ、C/EBP-α和FABP 4的蛋白水平。淫羊藿苷促进AA大鼠BMSCs增殖，并呈剂量依赖性。淫羊藿苷可下调AA大鼠BMSCs中p-p38/p38、p-JNK/JNK、p-ERK/ERK蛋白表达。淫羊藿苷可抑制AA大鼠骨髓基质细胞凋亡，使细胞周期阻滞于G/S期。淫羊藿苷对AA大鼠骨髓间充质干细胞的成脂作用也有抑制作用。而加入p38激动剂后，淫羊藿苷对BMSCs的作用减弱。结论淫羊藿苷通过抑制MAPK通路促进AA大鼠BMSCs增殖、抑制其凋亡和成脂。
Background Icariin, the main pharmacological active flavonoid extracted from Epimedi herba, can regulate cellular processes in diverse diseases. The aim of this study was to explore the effects and mechanisms of icariin on proliferation and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) in aplastic anemia (AA). Methods and results Bone marrow mesenchymal stem cells were isolated from posterior tibias and femurs of AA rats that were induced by benzene and cyclophosphamide and gavaged with icariin. The isolated BMSCs were characterized morphologically and immunologically by positive markers (CD29 and CD90) and negative markers (CD34 and CD45). CCK-8 assay was performed to examine the BMSCs proliferation. Cell apoptosis and cell cycle were detected by flow cytometry. Oil red O staining was carried out to evaluate the adipogenesis of BMSCs. The mRNA expression of PPAR gamma, C/EBP-alpha, and FABP4 was measured by qRT-PCR. The protein levels of p-p38/p38, p-JNK/JNK, p-ERK/ERK, PPAR gamma, C/EBP-alpha, and FABP4 were detected using Western blotting. Icariin promoted the proliferation of BMSCs from AA rats in a dose-dependent manner. The protein levels of p-p38/p38, p-JNK/JNK, and p-ERK/ERK were downregulated in BMSCs from AA rats after icariin treatment. Icariin inhibited the apoptosis and arrested cell cycle at G/S phase of BMSCs from AA rats. The adipogenesis of BMSCs from AA rats was also suppressed after icariin treatment. However, the effects of icariin on BMSCs were weakened by p38 agonist addition. Conclusions Icariin promoted the proliferation and inhibited the apoptosis and adipogenesis of BMSCs in AA by suppressing MAPK pathway.