Heparanase, an endo-glucuronidase that specifically cleaves heparan sulfate (HS), is upregulated in several pathological conditions. In this study, we aimed to find a correlation of heparanase expression and platelets production. In the transgenic mice overexpressing human heparanase (Hpa-tg), hematological analysis of blood samples revealed a significantly higher number of platelets in comparison with wild-type (Ctr) mice, while no significant difference was found in leukocytes and red blood cell number between the two groups. Total number of thiazole orange positive platelets was increased in Hpa-tg vs. Ctr blood, reflecting a higher rate of platelets production. Concomitantly, megakaryocytes from Hpa-tg mice produced more and shorter HS fragments that were shed into the medium. Further, thrombopoietin (TPO) level was elevated in the liver and plasma of Hpa-tg mice. Together, the data indicate that heparanase expression promoted megakaryopoiesis, which may be through upregulated expression of TPO and direct effect of released HS fragments expressed in the megakaryocytes.

中文翻译：

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乙酰肝素酶在小鼠中的过表达促进巨核细胞生成

肝素酶是一种特异性切割硫酸乙酰肝素（HS）的内切葡糖醛酸糖苷酶，在几种病理条件下均被上调。在这项研究中，我们旨在找到乙酰肝素酶表达与血小板产生的相关性。在过表达人乙酰肝素酶（Hpa-tg）的转基因小鼠中，血液样品的血液学分析显示，与野生型（Ctr）小鼠相比，血小板数量明显增加，而白细胞和红细胞数量之间没有显着差异。两组。与Ctr血液相比，Hpa-tg中噻唑橙阳性血小板的总数增加，反映出较高的血小板产生率。伴随而来的是，来自Hpa-tg小鼠的巨核细胞产生了更多和较短的HS片段，这些片段掉入了培养基中。进一步，Hpa-tg小鼠的肝脏和血浆中的血小板生成素（TPO）水平升高。总之，数据表明乙酰肝素酶表达促进了巨核细胞生成，这可能是通过TPO的表达上调和巨核细胞中表达的已释放HS片段的直接作用所致。