Data for Fig 2 from Novel elucidation and treatment of pancreatic chronic graft-versus-host disease in mice

Chronic graft-versus-host disease (cGVHD) is a severe complication of allogeneic haematopoietic stem cell transplantation. There is a growing understanding of cGVHD, and several effective therapies for cGVHD have been reported. However, pancreatic cGVHD is a potentially untapped study field. Our thought-provoking study using a mouse model of cGVHD suggested that the pancreas could be impaired by cGVHD-induced inflammation and fibrosis and that endoplasmic reticulum (ER) stress was augmented in the pancreas affected by cGVHD. These findings urged us to treat pancreatic cGVHD through reduction of ER stress, and we used 4-phenylbutyric acid (PBA) as an ER stress reducer. A series of experiments have indicated that PBA can suppress cGVHD-elicited ER stress in the pancreas and accordingly alleviate pancreatic cGVHD. Furthermore, we focused on a correlation between epithelial to mesenchymal transition (EMT) and fibrosis in the cGVHD-affected pancreas, because EMT was conceivably implicated in various fibrosis-associated diseases. Our investigation has suggested that the expression of EMT markers was increased in the cGVHD-disordered pancreas and that it could be reduced by PBA. Taken together, we have provided a clue to elucidate the pathogenic process of pancreatic cGVHD and created a potentially effective treatment of this disease using the ER stress alleviator PBA.慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植后的严重并发症。目前学界对cGVHD的认知不断深入，已有多项针对该病的有效治疗方案被报道。然而，胰腺型cGVHD仍是一个尚未得到充分挖掘的研究方向。本研究通过cGVHD小鼠模型开展实验，结果表明胰腺可因cGVHD诱导的炎症与纤维化受损，且受cGVHD累及的胰腺组织中内质网（ER）应激水平显著升高。上述发现促使我们尝试通过降低ER应激来干预胰腺型cGVHD，因此选用4-苯基丁酸（PBA）作为ER应激抑制剂。一系列实验证实，PBA可抑制胰腺组织中cGVHD诱发的ER应激，进而缓解胰腺型cGVHD的病情。此外，我们重点关注了cGVHD累及的胰腺组织中上皮间质转化（EMT）与纤维化的关联，因为EMT在多种纤维化相关疾病中均发挥着潜在作用。本研究进一步发现，cGVHD受累胰腺中EMT标志物的表达水平显著升高，且该升高现象可被PBA逆转。综上，本研究为阐明胰腺型cGVHD的致病机制提供了新思路，并借助ER应激缓解剂PBA开发了一种颇具潜力的该病治疗方案。