Effect of interrupted endogenous BMP/Smad signaling on growth and steroidogenesis of porcine granulosa cells

Bone morphogenetic proteins (BMPs) play a critical role in the growth and steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types. The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs. A strategy of RNA interference (RNAi)-mediated ‘gene silencing’ of Smad4, a core molecule mediating the intracellular BMP/Smad signal transduction pathways, was used to interrupt endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited growth, and induced apoptosis of porcine GCs, while decreasing estradiol production. In addition, interrupted BMP/Smad signaling significantly (P<0.05) changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.     

Berbamine inhibits proliferation and induces apoptosis of KU812 cells by increasing Smad3 activity

Objective  

The cytotoxic effect of berbamine on chronic myeloid leukemia (CML) cell line KU812 was evaluated, and the mechanisms of its action were explored.     

二甲双胍联合抗阻运动对糖尿病大鼠下丘脑TGF-β1-Smad2/3的影响

目的:探究二甲双胍联合抗阻运动干预对糖尿病大鼠的血糖的影响,以及对下丘脑TGF-β1、Smad2/3含量的影响。方法:采用高糖高脂饲料喂养结合腹腔注射链脲佐菌素(Streptozocin,STZ)注射液诱导糖尿病大鼠模型,二甲双胍和抗阻爬梯干预,Western-Blot法检测糖尿病大鼠下丘脑TGF-β1、Smad2/3蛋白表达量。结果:二甲双胍和运动均有一定降血糖效果,以药物治疗最为明显,联合干预的效果低于单独干预;二甲双胍和抗阻运动干预及其联合干预,Smad2/3、TGF-β1表达无明显的改变。结论:6周的糖尿病进程可能没有损伤大鼠下丘脑,抗阻运动和二甲双胍药物干预降低糖尿病大鼠血糖可能存在一定的抵消作用。     

Smad4基因在大肠癌中的表达及意义

目的：探讨Smad4基因在大肠癌中的表达及其与肿瘤分化程度或远处转移的关系。方法：利用免疫组织化学S～P法检测52例大肠癌组织、19例相应的癌旁正常组织中Smad4的表达。结果：Smad4在大肠癌原发灶中的阳性表达率为63．5％（33／52）,与癌旁正常组织中的阳性表达率89．5％（17／19）相比,Smad4阳性表达水平显著降低,差别有显著性（P〈0．05）;Smad4与肿瘤细胞分化程度无关（P〉0．05）,但与淋巴结转移显著相关（P〈0．05）。结论：Smad4的低表达可能是大肠癌发生过程的晚期事件,并可能通过直接或间接的作用促进大肠癌的淋巴结转移。     

不同运动方式对Ⅱ型糖尿病小鼠骨形成及BMPs/Smad途径相关分子表达的影响

摘要：目的：探究T2DM小鼠骨形成及BMPs/Smad途径中相关分子表达变化,以及不同力学刺激对T2DM小鼠骨形成及BMPs/Smad途径相关分子表达的影响。方法：40只4周龄雄性C57BL/6小鼠随机分为正常对照组(ZC)和T2DM组。T2DM组小鼠利用高脂膳食和STZ法进行T2DM造模,成功后将T2DM小鼠随机分为T2DM对照组(TC)、T2DM游泳组(TS)和T2DM下坡跑组(TD),并利用游泳和下坡跑分别对TS和TD组小鼠进行8周运动干预。结束后,利用ALP染液对其骨形成能力进行检测;利用RT-PCR法检测右侧胫骨中相关因子mRNA表达;利用West-blotting法检测右侧股骨中相关因子蛋白表达。结果：与ZC组相比,TC组小鼠骨湿重(P＜0.01)和松质骨数量及形态结构均显著下降,OB和颅骨骨形成能力下降;与TC组相比,TS组松质骨数量和形态结构均增加,OB和颅骨骨形成能力升高;与TS组相比,TD组松质骨数量和形态结构均增加,OB和颅骨骨形成能力显著升高。结论：T2DM小鼠骨形成及BMPs/Smad途径被抑制;下坡跑对T2DM小鼠骨产生的直接作用力通过激活BMPs/Smad途径,促进骨形成,改善骨组织形态结构和骨湿重,且其效果优于游泳产生的间接作用力。