遗传谱系追踪揭示星状细胞是胰腺和胰岛纤维化中肌成纤维细胞的来源。

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Wang Jinbang, Li Tingting, Zhou Yunting, Wang Xiaohang, Carvalho Vladmir, Ni Chengming, Li Wei, Wang Qianqian, Chen Yang, Shang Zhanjia, Qiu Shanhu, Sun Zilin

Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.

Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

iScience. 2023 May 26;26(6):106988. doi: 10.1016/j.isci.2023.106988. eCollection 2023 Jun 16.

Pancreatic stellate cells (PSCs) are suggested to play an important role in the development of pancreas and islet fibrosis. However, the precise contributions and solid evidence of PSCs to the fibrogenesis remain to be elucidated. Here, we developed a novel fate-tracing strategy for PSCs by vitamin A administration in Lrat-cre; Rosa26-tdTomato transgenic mouse. The results showed that stellate cells give rise to 65.7% of myofibroblasts in cerulein-induced pancreatic exocrine fibrosis. In addition, stellate cells in islets increase and contribute partly to myofibroblasts pool in streptozocin-induced acute or chronic islet injury and fibrosis. Furthermore, we substantiated the functional contribution of PSCs to fibrogenesis of pancreatic exocrine and islet in PSCs ablated mice. We also found stellate cells' genetic ablation can improve pancreatic exocrine but not islet fibrosis. Together, our data indicates that stellate cells are vital/partial contributors to myofibroblasts in pancreatic exocrine/islet fibrosis.

胰腺星状细胞（PSCs）被认为在胰腺和胰岛纤维化的发展中起重要作用。然而，PSCs对纤维化形成的确切贡献和确凿证据仍有待阐明。在此，我们通过在Lrat-cre；Rosa26-tdTomato转基因小鼠中给予维生素A，开发了一种针对PSCs的新型命运追踪策略。结果显示，在雨蛙肽诱导的胰腺外分泌纤维化中，星状细胞产生了65.7%的肌成纤维细胞。此外，在链脲佐菌素诱导的急性或慢性胰岛损伤及纤维化中，胰岛中的星状细胞增加并部分促成了肌成纤维细胞库。此外，我们证实了PSCs对PSCs消融小鼠胰腺外分泌和胰岛纤维化形成的功能贡献。我们还发现星状细胞的基因消融可改善胰腺外分泌纤维化，但不能改善胰岛纤维化。总之，我们的数据表明，星状细胞是胰腺外分泌/胰岛纤维化中肌成纤维细胞的重要/部分贡献者。