外泌体介导HPV16感染合并抑郁症的分子机制研究

High risk human papillomavirus infection is seriouly harmful to human health, resulting in organic lesion, depression, and adverse effect on prognosis. To identify definite pathogenic factor of high risk human papillomavirus infection with depression, and explore the molecular mechanisms of pathopoiesis, is very important for clinical diagnosis and treatment. Previous studies indicated that exosome derived from HPV16 E6/E7 positive TC-1 cell, inhibited neural stem cells differentiation to mature nerve cells. Exosome derived from target cells could regulate nervous system. So, exosome derived from HPV16 E6/E7 positive TC-1 cell may have an affect on specific regions of the brain resulting in depression, from the fluid circulation to the brain. To study the effect on neuropsychological dysfunction of exosome derived from TC-1 cell, molecular mechanism of exosome inducing depression after HPV16 infection could be resolved. Exosome production will be prevented and specific pathogenic factor of depression derived from exosome will be blocked, for the treatment of HPV16 infection with depression. Theoretical basis for new method for clinical diagnosis and treatment could be established.

高危型HPV16型感染严重危害人类健康,除了导致器质性病变以外，还可能合并抑郁症等心理障碍，对预后产生不良影响。明确介导HPV感染合并抑郁症发生的致病因子、探索其致病的分子机制，对于疾病的临床诊疗极为重要。课题组前期研究发现，HPV16 E6/E7阳性的TC-1细胞分泌的外泌体具有抑制神经干细胞向成熟神经细胞分化的功能，说明靶细胞产生的外泌体对神经系统具有一定的调节作用。提示HPV16 E6/E7阳性的TC-1细胞来源的外泌体可能经体液循环至脑部，对脑部特定区域产生影响，导致抑郁症状的出现。本次课题拟通过研究TC-1细胞外泌体对神经精神功能障碍的影响，明确外泌体在高危型HPV感染合并抑郁症中所起的具体作用，解析外泌体诱发HPV16感染合并抑郁症的分子机制；并探索通过阻止外泌体产生、阻断外泌体内特异性致抑郁因子来治疗HPV16感染合并抑郁症的可行性，为临床诊疗新方法的确立奠定理论基础。

高危型HPV16型感染严重危害人类健康,除了导致器质性病变以外，部分患者合并抑郁症等心理障碍，对预后产生不良影响。课题组研究发现，HPV16 E6/E7阳性的TC-1细胞分泌的外泌体具有抑制神经干细胞向成熟神经细胞分化的功能，提示了靶细胞产生的外泌体对神经系统具有一定的调节作用。进一步证实了HPV16 E6/E7阳性的TC-1细胞来源的外泌体经体液循环至脑部，对脑部特定区域产生影响，导致抑郁症状的出现。本次课题解析了外泌体诱发HPV16感染合并抑郁症的分子机制；并探索了通过阻止外泌体产生、阻断外泌体内特异性致抑郁因子来治疗HPV16感染合并抑郁症的可行性，为临床诊疗新方法的确立奠定了理论基础。