Abbasi Parvaneh, Shamsasenjan Karim, Movassaghpour Akbari Ali Akbar, Akbarzadehlaleh Parvin, Dehdilani Nima, Ejtehadifar Mostafa
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Cell J. 2015 Spring;17(1):15-26. doi: 10.22074/cellj.2015.508. Epub 2015 Apr 8.
The peroxisome proliferator-activated receptors (PPARs) are a group of nu- clear receptor proteins whose functions as transcription factors regulate gene expres- sions. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. This study attempts to determine the effect of baicalin, a PPARγ activator, on erythroid differentiation of cluster of differentiation 133(+)(CD133(+)) cord blood hematopoietic stem cells (HSCs).
In this experimental study, in order to investigate the effects of the PPARγ agonists baicalin and troglitazone on erythropoiesis, we isolated CD133(+) cells from human umbilical cord blood using the MACS method. Isolated cells were cultured in erythroid-inducing medium with or without various amounts of the two PPARγ activa- tors (baicalin and troglitazone). Erythroid differentiation of CD133(+)cord blood HSCs were assessed using microscopic morphology analysis, flow cytometric analysis of erythroid surface markers transferrin receptor (TfR) and glycophorin A (GPA) and bycolony forming assay.
Microscopic and flow cytometric analysis revealed the erythroid differentiation of CD133(+)cord blood HSCs under applied erythroid inducing conditions. Our flow cytometric data showed that the TfR and GPA positive cell population diminished significantly in the presence of either troglitazone or baicalin. The suppression of erythroid differentiation in response to PPARγ agonists was dose-dependent. Erythroid colony-forming ability of HSC decreased significantly after treatment with both PPARγ agonists but troglitazone had a markedly greater effect.
Our results have demonstrated that PPARγ agonists modulate erythroid dif- ferentiation of CD133(+)HSCs, and therefore play an important role in regulation of normal erythropoiesis under physiologic conditions. Thus, considering the availability and applica- tion of this herbal remedy for treatment of a wide range of diseases, the inhibitory effect of baicalin on erythropoiesis should be noted.
过氧化物酶体增殖物激活受体（PPARs）是一类核受体蛋白，作为转录因子调节基因表达。PPARs在高等生物的细胞分化、发育和代谢（碳水化合物、脂质、蛋白质）以及肿瘤发生的调节中发挥重要作用。本研究旨在确定PPARγ激活剂黄芩苷对分化簇133（+）（CD133（+））脐带血造血干细胞（HSCs）红系分化的影响。
在本实验研究中，为了研究PPARγ激动剂黄芩苷和曲格列酮对红细胞生成的影响，我们使用磁珠分选法从人脐带血中分离出CD133（+）细胞。将分离出的细胞在含有或不含有不同剂量的两种PPARγ激活剂（黄芩苷和曲格列酮）的红系诱导培养基中培养。使用显微镜形态学分析、红系表面标志物转铁蛋白受体（TfR）和血型糖蛋白A（GPA）的流式细胞术分析以及集落形成试验评估CD133（+）脐带血HSCs的红系分化。
显微镜和流式细胞术分析显示，在应用的红系诱导条件下，CD133（+）脐带血HSCs发生了红系分化。我们的流式细胞术数据表明，在曲格列酮或黄芩苷存在的情况下，TfR和GPA阳性细胞群体显著减少。PPARγ激动剂对红系分化的抑制作用呈剂量依赖性。两种PPARγ激动剂处理后，HSC的红系集落形成能力均显著降低，但曲格列酮的作用明显更强。
我们的结果表明，PPARγ激动剂可调节CD133（+）HSCs的红系分化，因此在生理条件下正常红细胞生成的调节中发挥重要作用。因此，考虑到这种草药疗法在治疗多种疾病中的可用性和应用，应注意黄芩苷对红细胞生成的抑制作用。
