| First Author | Chen H | Year | 2020 |
| Journal | J Cell Mol Med | Volume | 24 |
| Issue | 2 | Pages | 1488-1503 |
| PubMed ID | 31797546 | Mgi Jnum | J:306449 |
| Mgi Id | MGI:6706172 | Doi | 10.1111/jcmm.14833 |
| Citation | Chen H, et al. (2020) Hic-5 deficiency protects cerulein-induced chronic pancreatitis via down-regulation of the NF-kappaB (p65)/IL-6 signalling pathway. J Cell Mol Med 24(2):1488-1503 |
| abstractText | Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide-inducible clone-5 (Hic-5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic-5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic-5 was significant up-regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic-5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic-5 KO mice was significantly attenuated. We also found that the Hic-5 up-regulation by cerulein activated the NF-kappaB (p65)/IL-6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as alpha-SMA and Col1a1. Therefore, we determined whether suppressing NF-kappaB/p65 alleviated CP by treating mice with the NF-kappaB/p65 inhibitor triptolide in the cerulein-induced CP model and found that pancreatic fibrosis was alleviated by NF-kappaB/p65 inhibition. These findings provide evidence for Hic-5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis. |
