血浆外泌体miR-26b-3p调控生长板自噬和SMAD3/TGF-β信号通路介导特发性矮小症的机制研究

特发性矮小症（ISS)的病因不清，缺乏有效诊断和治疗。申请人将ISS患者血浆外泌体与人软骨细胞共同培养，细胞出现增殖、分化和骨化障碍。基因芯片和qPCR检测发现ISS的血浆外泌体miR-26b-3p呈高表达。过表达miR-26b-3p后软骨细胞同样出现增殖、分化和骨化障碍。siRNA沉默外泌体过表达miR-26b-3p后，软骨细胞功能恢复。过表达miR-26b-3p细胞mRNA芯片发现下游候选靶基因ATG5和SMAD3降低，后qPCR证实。据此，课题组提出假说：循环血液中外泌体miR-26b-3p高表达，通过入胞作用下调生长板软骨细胞ATG5和SMAD3表达，抑制自噬和TGF-β信号通路，阻滞生长板正常发育，导致ISS身材矮小。我们拟通过RIP等技术，进一步揭示循环血液外泌体miR-26b-3p异常表达在ISS发病过程中的作用机制，为通过生物学技术实施早期诊断和治疗ISS提供理论和新思路。

Idiopathic short stature (ISS) is the main cause of short stature. The etiology of ISS is unclear, and it is lack of effective diagnosis and treatment, which seriously affects the physical and mental health of children.The applicant cultured the plasma exosomes of ISS patients together with human chondrocytes, and the cells showed proliferation, differentiation and ossification obstacles. The high expression of mir-26b-3p in ISS was detected by microarray and qPCR. Over expression of mir-26b-3p also resulted in proliferation, differentiation and ossification of chondrocytes. The function of chondrocytes recovered after siRNA silenced the overexpression of mir-26b-3p in exosomes. The down stream candidate genes ATG5 and Smad3 were found to be down regulated by over expression of mir-26b-3p cell mRNA chip, which was confirmed by qPCR. According to this, the research team put forward the hypothesis: the high expression of mir-26b-3p in exosomes in circulating blood, through the effect of endocytosis, down regulate the expression of ATG5 and Smad3 in growth plate chondrocytes, inhibit autophagy and TGF - β signal pathway, block the normal development of growth plate, and cause ISS short stature. We intend to further reveal the mechanism of abnormal expression of mir-26b-3p in exocrine body of circulating blood in the pathogenesis of ISS by rip and other technologies, so as to provide theory and new ideas for early diagnosis and treatment of ISS by biological technology.