Dataset Information

SMAD3/Stat3 Signaling Mediates ?-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes.

ABSTRACT: Many patients with chronic pancreatitis develop diabetes (chronic pancreatitis-related diabetes [CPRD]) through an undetermined mechanism. Here we used long-term partial pancreatic duct ligation (PDL) as a model to study CPRD. We found that long-term PDL induced significant ?-cell dedifferentiation, followed by a time-dependent decrease in functional ?-cell mass-all specifically in the ligated tail portion of the pancreas (PDL-tail). High levels of transforming growth factor ?1 (TGF?1) were detected in the PDL-tail and were mainly produced by M2 macrophages at the early stage and by activated myofibroblasts at the later stage. Loss of ?-cell mass was then found to result from TGF?1-triggered epithelial-mesenchymal transition (EMT) by ?-cells, rather than resulting directly from ?-cell apoptosis. Mechanistically, TGF?1-treated ?-cells activated expression of the EMT regulator gene Snail in a SMAD3/Stat3-dependent manner. Moreover, forced expression of forkhead box protein O1 (FoxO1), an antagonist for activated Stat3, specifically in ?-cells ameliorated ?-cell EMT and ?-cell loss and prevented the onset of diabetes in mice undergoing PDL. Together, our data suggest that chronic pancreatitis may trigger TGF?1-mediated ?-cell EMT to lead to CPRD, which could substantially be prevented by sustained expression of FoxO1 in ?-cells.

SUBMITTER: Xiao X

PROVIDER: S-EPMC5606322 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes.

Xiao Xiangwei X Fischbach Shane S Zhang Tina T Chen Congde C Sheng Qingfeng Q Zimmerman Ray R Patnaik Sneha S Fusco Joseph J Ming Yungching Y Guo Ping P Shiota Chiyo C Prasadan Krishna K Gangopadhyay Nupur N Husain Sohail Z SZ Dong Henry H Gittes George K GK

Diabetes 20170803 10

Many patients with chronic pancreatitis develop diabetes (chronic pancreatitis-related diabetes [CPRD]) through an undetermined mechanism. Here we used long-term partial pancreatic duct ligation (PDL) as a model to study CPRD. We found that long-term PDL induced significant β-cell dedifferentiation, followed by a time-dependent decrease in functional β-cell mass-all specifically in the ligated tail portion of the pancreas (PDL-tail). High levels of transforming growth factor β1 (TGFβ1) were dete ...[more]

PMID: 28775125

Similar Datasets

Project description:BackgroundCigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.MethodsThe present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.ResultsBased on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.ConclusionsIn summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

Dataset Information

SMAD3/Stat3 Signaling Mediates ?-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes.

Publications

SMAD3/Stat3 Signaling Mediates β-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets