结果显示,与对照组比较,GW501516可诱导人脐静脉内皮细胞(HUVEC)中PAI-1表达,且此效应呈浓度和时间依赖性(P<0.05);siRNA沉默PPARδ的表达后,可阻抑GW501516对HUVEC细胞PAI-1表达的促进作用;TGFβ-Smad3信号通路抑制剂SB-431542与SIS3均可降低HUVEC细胞pSmad3蛋白的表达,而细胞PAI-1表达也随之降低.结果提示,GW501516可促进HUVEC细胞PAI-1的表达,其机制可能与TGFβ-Smad3信号通路有关.
目的:观察转化生长因子-β1受体1对肾阳虚不育模型大鼠血清性激素水平、精子质量以及细胞色素P-19表达的影响。方法:40只SD大鼠随机分为4组:空白对照组、模型组、正常+阻滞组及模型+阻滞剂组,每组10只。采用腺嘌呤诱导肾阳虚不育模型,在解剖显微镜下,对阻滞组大鼠睾丸间质内进行显微注射。采用放射免疫法检测各组大鼠性激素水平;精子自动检测仪检测精子的密度及活率;用免疫组织化学法检测大鼠睾丸中TGF-β1/CYP19表达。结果:与模型组相比,正常+阻滞组和模型+阻滞剂组睾酮(Testosterone,T)和雌二醇(Estradiol
2,E2)水平均显著升高(P<0.05),大鼠精子密度和精子活率以及快速前向运动精子率(A级)、满速前向运动精子率(B级)显著上升(P<0.05),睾丸CYP19水平均显著升高(P0.05);与模型组相比,正常+阻滞组和模型+阻滞剂组TGF-β1均有降低(P0.05)。结论:TGF-βR1在睾丸表达异常与肾阳虚不育模型大鼠精子质量提高和血清性激素水平改变有关。
Multiple Selleck Canertinib myeloma is
a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased selleck产品 osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute
to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple 无 OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.