Sox9 is required in regeneration of pancreatic β cells following injury.
Sox9 is required in regeneration of pancreatic β cells following injury.
复制标题
DOI：
10.1016/j.yexcr.2022.113406
复制
发表时间：
2022-11
影响因子：
3.7
通讯作者：
Qi Wang;Jinhui Chen;Jing Han;Zhe Yang;Yanping Yang;Hong Li;Shumin Wang;Yan Hong
中科院分区：
文献类型：
--
作者：
Qi Wang;Jinhui Chen;Jing Han;Zhe Yang;Yanping Yang;Hong Li;Shumin Wang;Yan Hong
自身免疫反应导致胰岛β细胞损伤导致胰岛素分泌减少是1型糖尿病（T1 DM）的病理基础。因此，寻找新的减轻胰岛β细胞损伤的分子靶点，将为T1 DM的防治提供实验依据。SRY-box 9（Sox 9）不仅是调控各种器官发育的重要分子，而且其高表达可加重各种疾病的病理过程。此外，Sox 9+细胞也是胰腺祖细胞，参与损伤诱导的胰腺修复反应。在我们的研究中，在链脲佐菌素（STZ）诱导的胰腺β细胞损伤后，随着时间的推移，血糖升高和胰腺β细胞缺乏几乎恢复正常，这意味着胰腺β细胞在STZ诱导的损伤后再生。特别地，Sox 9的表达在胰腺β细胞再生期间显著升高。在此基础上，我们进行了体外实验，验证过表达Sox 9是否能够抑制炎症因子对胰腺β细胞的损伤。结果表明，Sox 9过表达可减轻炎症因子对胰岛β细胞的损伤，增强炎症因子对胰岛β细胞胰岛素分泌的抑制作用。不出所料，在用STZ治疗胰腺β细胞特异性敲除Sox 9小鼠后，血糖水平、胰岛素含量和胰腺β细胞数量未能及时恢复到接近正常水平，进一步证实了Sox 9在促进胰腺β细胞修复或再生中的重要性。提示Sox 9活性增强可能对自身免疫性损伤的胰岛β细胞有保护作用，从而改善T1 DM的病理过程。
The reduction of insulin secretion due to pancreatic β cell injury caused by autoimmune reaction is the pathological basis of Type 1 diabetes mellitus (T1DM). Therefore, seeking new molecular targets for alleviating pancreatic β cell injury will provide experimental basis for the prevention and treatment of T1DM. SRY-box 9 (Sox9) is not only an important molecule regulating the development of various organs, but also its high expression can aggravate the pathological process of various diseases. In addition, Sox9+cells are also pancreatic progenitor cells, participating in pancreatic repair reaction induced by injury. In our study, elevated blood glucose and lack of pancreatic β cells almost returned to normal over time after streptozotocin (STZ)-induced pancreatic β cell damage, implying that pancreatic β cells were regenerated after STZ-induced injury. In particular, the expression of Sox9 was significantly elevated during pancreatic β cell regeneration. On this basis, we conducted in vitro experiments to verify whether overexpression of Sox9 could inhibit the damage of pancreatic β cells by inflammatory factors. Our results showed that overexpression of Sox9 alleviated the damage of pancreatic β cells by inflammatory factors and improved the inhibitory effect of inflammatory factors on insulin secretion of pancreatic β cells. Unsurprising, blood glucose levels, insulin content and pancreatic β cell number failed to return to near-normal levels timely after pancreatic β cells specific knockout Sox9 mice were treated with STZ, further confirming the importance of Sox9 in facilitating pancreatic β cell repair or regeneration. Our study indicate that enhanced Sox9 activity might protect pancreatic β cells from autoimmune induced damage and thus improve the pathological process of T1DM.