HMGN2调控雌激素介导的膀胱粘膜屏障结构与功能改变

我们首先报道了核因子HMGN2具有抗菌、抗病毒新功能，新近我们发现干扰HMGN2基因后，在转录水平上雌激素信号级联、粘膜上皮屏障结构或效应基因如细胞连接蛋白、抗菌肽等基因出现明显改变，且上述改变之间存在符合生物学理论的逻辑联系；HMGN2还可改变膀胱上皮细胞骨架微丝聚合，减少细菌粘附侵袭细胞。结合国内外HMG分子与雌激素信号级联间的关系及其对粘膜屏障防御能力影响研究进展分析，我们提出HMGN2可能参与调控雌激素介导的膀胱粘膜屏障结构功能改变的假设。为此我们将从粘膜机械、免疫屏障两个角度，在细胞、动物和临床三个层面，验证HMGN2是否通过雌激素信号级联，影响膀胱粘膜抗菌肽、炎症趋化因子及与细胞分化、细胞间连接相关效应分子产生，最终调节膀胱粘膜机械和免疫屏障结构与功能，减少细菌粘附侵袭。其结果将有助于揭示HMGN2在膀胱粘膜屏障结构与功能调节中所起的重要作用，也有助于深入理解粘膜屏障防御机制。

We first reported that nuclear factor HMGN2 possessed anti-microbial and anti-viral effects. More recently, we also found that there were significant changes on estrogen signaling cascade, mucosal epithelial barrier related genes in HMGN2 knockdown cells, such as cell junction proteins and antimicrobial peptides. And these changes conform to biological logical theory; HMGN2 also changes urothelial cytoskeletal actin polymerization, reduces bacterial adhesion and invasion of cells. In accordance with other research progress in the relationship with HMG molecular and estrogen signaling cascade, and its impact on the mucosal barrier defense capability analysis.We propose HMGN2 may be involved in regulating the structure and function of estrogen-mediated changes in bladder mucosal barrier. Therefore we expect to demonstrate HMGN2 may affect the bladder mucosal antimicrobial peptides, inflammatory chemokines and cell differentiation or cell junction molecules through estrogen signaling cascade, which is important to regulate the structure and function of bladder mucosa mechanical and immunological barrier to reduce bacterial adhesion and invasion . The results will help to reveal the important role of HMGN2 in regulating the structure and function of bladder mucosal barrier, which is also significant to understanding the mechanisms of mucosal barrier defense.