小鼠乳腺增生组织中BMP信号通路的改变

Changes of BMP signaling pathway in mammary glands of mice with mammary hyperplasia

目的:探明骨形态发生蛋白(BMP)信号分子在乳腺增生组织中的表达模式和BMP通路的激活情况。方法:8周龄的未孕雌性C57BL/C小鼠按体重随机分为2组:对照组和激素组,每组15只。激素组先以2.5mg/kg的戊酸雌二醇灌胃25 d,再腹腔注射黄体酮(4 mg/kg)5 d诱导乳腺增生;对照组予以等体积的PBS。给药结束后收集乳腺组织,观察乳腺的形态,real-time PCR检测BMP信号分子的表达水平,并用Western blot检测Smad1/5/9的磷酸化水平。结果:与对照组比较,在乳腺增生组织中,BMP信号通路配体BMP2、4、5、6、7、9、13和14,受体BMPR1A及拮抗剂Chrdl1和Twsg1的表达异常(P<0.05);而BMP3、BMP12、BMPR1B、BMPR2、Chrd、Chrdl2和Noggin等分子的表达则无明显改变;Western blot结果显示乳腺增生组织的Smad1/5/9的磷酸化水平升高(P<0.05)。结论:多个BMP信号分子在乳腺增生组织中异常表达,致使BMP通路异常激活。BMP信号通路可能成为治疗乳腺增生的新靶点。

AIM:To determine the expression patterns of bone morphogenetic protein(BMP)signaling components in the mammary glands with hyperplasia(MGH)and the activation of this signaling pathway.METHODS:The female C57BL/C mice(8-weeks-old)were randomly divided into control group and hormone group with15mice in each group.The mice in control group were treated with PBS,while the mice in hormone group were intragastric administration with estradiol valerate(2.5mg/kg)for25d,followed by progesterone(4mg/kg)peritoneal injection for5d.At the end of treatments,the mammary glands were collected to determine the morphological changes,the mRNA expression of BMP signaling components and the phosphorylation level of Smad1/5/9.RESULTS:In MGH,a part of BMP signaling pathway molecules were differentially expressed(P<0.05),including BMP ligands BMP2,4,5,6,7,9,13and14,BMP receptor BMPR1A,and antagonists Chrdl1and Twsg,whereas the expression levels of some molecules,such as BMP3,BMP12,BMPR1B,BMPR2,Chrd,Chrdl2and Noggin,were not altered.The phosphorylation levels of Smad1/5/9was up-regulated in MGH(P<0.05).CONCLUSION:BMP signaling pathway is activated in MGH through the abnormal expression of its components.BMP signaling pathway may be a new target for MGH therapy.