title: Activation of pancreatic stellate cells involves an EMT-like process.
abstract: Pancreatic adenocarcinoma (PDAC) and chronic pancreatitis (CP) are characterized by a desmoplastic reaction involving activated pancreatic stellate cells (PSCs). However, the mechanisms of PSC activation remain poorly understood. We examined whether the epithelial-mesenchymal transition (EMT) process might play a role in PSC activation. PSCs were isolated from a rat pancreas and characterized using immunofluorescence and immunocytochemistry. We evaluated changes in cell motility and in the expression levels of a panel of EMT-related genes during the PSC activation process. Activation of PSCs occurred after 48 h of in vitro culture, as indicated by a morphological change to a myofibroblastic shape and a decrease in the number of cytoplasmic lipid droplets. After activation, PSCs showed enhanced cell migration ability compared to quiescent cells. In addition, the expression of epithelial markers (E-cadherin, BMP7 and desmoplakin) decreased, while expression of mesenchymal markers (N-cadherin, vimentin, fibronectin1, collagen1α1 and S100A4) increased in activated PSCs. EMT-related transcription factors (Snail and Slug) were also upregulated after PSC activation. The concurrent increase in cell migration ability and alterations in EMT-related gene expression suggests that the activation of PSCs involves an EMT-like process. The knowledge that PSC activation involves an EMT‑like process may help to identify potential new therapeutic targets to alleviate pancreatic fibrosis in diseases like CP and PDAC.
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Zi-Peng
authors.initials: ZP
authors.lastname: Lu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Bao-Bao
authors.initials: BB
authors.lastname: Cai
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Liang-Tao
authors.initials: LT
authors.lastname: Zhao
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Qing-Cheng
authors.initials: QC
authors.lastname: Xu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Du
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Pancreas Institute of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Kui-Rong
authors.initials: KR
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D051180:Desmoplakins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D015820:Cadherins; D051180:Desmoplakins; D014157:Transcription Factors