☆ 4.6 Review

Acinar cells and the development of pancreatic fibrosis

CYTOKINE & GROWTH FACTOR REVIEWS (2023)

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Loss of acinar cell VMP1 triggers spontaneous pancreatitis in mice

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Summary: VMP1 plays a crucial role in the pathogenesis of pancreatitis by regulating autophagic degradation and ER stress, and its deficiency promotes inflammation and fibrosis. The study revealed the importance of VMP1 in modulating pancreatitis through the NFE2L2/Nrf2 pathway.

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Article Oncology

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

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Summary: This study investigated the potential role of histological chronic pancreatitis findings and chronic inflammation in surgical pancreatic ductal adenocarcinoma (PDAC) specimens on disease-specific survival (DSS). The results suggest that more severe fibrosis, acinar atrophy, and chronic inflammation in the pancreatic stroma were associated with worse DSS outcomes for PDAC patients.

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The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer

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Summary: This article discusses the importance of the Hippo signaling pathway in cancer research and explores recent discoveries on how this pathway influences cancer progression. It also focuses on the latest efforts to target the key effectors of the pathway for therapeutic purposes in both preclinical and clinical settings.

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Article Gastroenterology & Hepatology

Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury

Zhibo Ma et al.

Summary: Under chronic injury conditions, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and enteroendocrine cell lineages. ADM-derived enteroendocrine cell subtypes are diverse. Expression of Kras(G12D) is sufficient to drive neoplasia when targeted to injury-induced ADM populations, providing an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, shedding light on early events in pancreatic diseases.

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Anna R. Jussila et al.

Summary: This study identifies the Wnt/DPP4 axis as a key driver of fibrosis and fat loss, providing potential therapeutic targets for intervention.

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Intra-pancreatic fat deposition: bringing hidden fat to the fore

Maxim S. Petrov et al.

Summary: Fatty pancreas disease is a common condition that not only affects physical health, but is also associated with the development of multiple diseases. Research has shown that weight loss can alleviate symptoms of type 2 diabetes, and reversing fatty pancreas disease may prevent or intercept the progression of major pancreatic diseases in the future.

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St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis

Rong-chang Cao et al.

Summary: This study investigates St13 as a potential therapeutic target in chronic pancreatitis (CP) and demonstrates its role in regulating the arachidonic acid pathway to protect against pancreatic damage. Additionally, it validates the value of Ga-68-FAPI-04 PET/CT for the early diagnosis of CP.

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YAP activates pancreatic stellate cells and enhances pancreatic fibrosis

Lennard Spanehl et al.

Summary: Activated YAP enhances PSCs proliferation, and the antifibrotic potential of Hippo pathway inhibitors deserves further investigation.

HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL (2022)

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Lutein inhibits IL-6 expression by inducing PPAR-γ activation and SOCS3 expression in cerulein-stimulated pancreatic acinar cells

Yu Jin Ahn et al.

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Jiaqi Liu et al.

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Ghrelin inhibits IKKβ/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein

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Summary: The study found a correlation between serum ghrelin concentration and the severity of acute pancreatitis. In animal models, ghrelin may play a protective role in the pathogenesis of acute pancreatitis by inhibiting pro-inflammatory cytokines and the activation of the IKK beta/NF-kappa B signaling pathway.

HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL (2021)

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mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote KrasG12D-Induced Acinar-to-Ductal Metaplasia and Early Pancreatic Carcinogenesis

Yamin Zhao et al.

Summary: mTORC1 and mTORC2 play a dual, nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting the function of the Arp2/3 complex. The Arp2/3 complex acts as a common effector of mTORC1 and mTORC2, connecting oncogenic signals with actin dynamics in PDAC initiation.

GASTROENTEROLOGY (2021)

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The Role of PPAR-γ in Allergic Disease

Julian M. Stark et al.

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The effects of nuclear factor-kappa B in pancreatic stellate cells on inflammation and fibrosis of chronic pancreatitis

Nan Wu et al.

Summary: The study indicates that TGF-β1 can induce the activation of the NF-κB pathway in PSCs by regulating p-TAK1, and the NF-κB pathway in PSCs may be a target of chronic inflammation and fibrosis.

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Recent advances in tissue stem cells

Xin Fu et al.

Summary: Stem cells are crucial undifferentiated cells with the ability of self-renewal and differentiation, playing a significant role in organ and tissue development and repair. Tissue-specific stem cells hold powerful potential for regeneration and are promising for future research in tissue stem cell biology.

SCIENCE CHINA-LIFE SCIENCES (2021)

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PTHrP Drives Pancreatic Cancer Growth and Metastasis and Reveals a New Therapeutic Vulnerability

Jason R. Pitarresi et al.

Summary: The amplification of PTHrP in pancreatic cancer is related to tumor growth and metastasis, and its loss can significantly reduce tumor burden, eliminate metastasis, and enhance overall survival. Targeting PTHrP activity may be a novel therapeutic approach for treating pancreatic cancer.

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Regulation of Pancreatic Fibrosis by Acinar Cell-Derived Exosomal miR-130a-3p via Targeting of Stellate Cell PPAR-γ

Qiang Wang et al.

Summary: This study revealed that exosomal miR-130a-3p promotes PSC activation and collagen formation by targeting PPAR-gamma. Knock-down of miR-130a-3p significantly improved pancreatic fibrosis, reduced serum levels of HA and beta-amylase, and increased C-peptide levels. The exosomal miR-130a-3p/PPAR-gamma axis could be a potential new target for the treatment of chronic pancreatic fibrosis.

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MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions

Elyne Backx et al.

Summary: This study transcriptionally profiled the two major human pancreatic exocrine cell types, acinar and duct cells, during experimental stress conditions. The results showed that in dedifferentiated acinar cells, cancer pathways are upregulated in which MECOM is a critical regulator that suppresses acinar cell death by permitting cellular dedifferentiation.

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Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids

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PPAR? drives IL-33-dependent ILC2 pro-tumoral functions

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Editorial Material Cell & Tissue Engineering

Pancreatic plasticity: Unlocking exocrine lineage specification

Jason R. Pitarresi et al.

Summary: In this issue, two studies developed human stem-cell-derived organoid culture systems to mimic pancreatic acinar and ductal lineages, offering opportunities to study cellular plasticity and transformation in pancreatic cancer initiation and progression.

CELL STEM CELL (2021)

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Article Gastroenterology & Hepatology

Novel Circulating and Tissue Monocytes as Well as Macrophages in Pancreatitis and Recovery

Murli Manohar et al.

Summary: The study identified several novel monocyte/macrophage subsets with unique phenotype and functional characteristics associated with acute pancreatitis (AP), recovery, and severe acute pancreatitis (SAP). The findings highlight the differential innate immune responses during AP progression and recovery that can be valuable for future disease monitoring and targeting.

GASTROENTEROLOGY (2021)

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Article Biochemistry & Molecular Biology

Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice

Ziqi Zhou et al.

Summary: Acute pancreatitis (AP) is an inflammatory disorder, and research shows that Betulinic acid (BA) has prophylactic and therapeutic effects on AP. BA can reduce the severity of pancreatitis, decrease inflammation, and inhibit the NF-κ B signaling pathway.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

Min Seung Kwak et al.

Summary: Obesity increases the incidence of acute pancreatitis and induces the adipocytokine resistin, which in turn aggravates the expression of the proinflammatory mediator IL-6. Astaxanthin (ASX) has been found to inhibit IL-6 expression by reducing calcium overload and oxidative stress caused by resistin in pancreatic acinar cells.

MEDIATORS OF INFLAMMATION (2021)

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Article Multidisciplinary Sciences

Acinar cell clonal expansion in pancreas homeostasis and carcinogenesis

Patrick Neuhofer et al.

Summary: Studies have identified a rare TERT-positive subpopulation of acinar cells in the pancreas that play a role in pancreatic renewal and potential initiation of PDAC. Expression of mutant Kras in these TERT-high acinar cells accelerates acinar clone formation and transdifferentiation, highlighting their potential role in pancreatic tumorigenesis as early cancer precursor lesions.

NATURE (2021)

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David Montaigne et al.

Summary: Novel PPAR agonists offer new opportunities for managing metabolic and cardiovascular diseases by regulating gene expression, lipid metabolism, insulin sensitivity, glucose metabolism, and cardiovascular health. Activation of PPARs by specific ligands can have antiatherogenic, anti-inflammatory, and metabolic benefits, making them important therapeutic targets in the treatment of various diseases.

NATURE REVIEWS CARDIOLOGY (2021)

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Review Biochemistry & Molecular Biology

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Summary: Wnt/β-catenin signaling plays a critical role in human cancers, associated with cancer progression, prognosis, and mortality. Despite the development of therapies targeting this pathway, there are challenges in translating them into clinical practice.

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Akt1 signalling supports acinar proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

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Anisodamine alleviates lipopolysaccharide-induced pancreatic acinar cell injury through NLRP3 inflammasome and NF-κB signaling pathway

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JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION (2020)

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Serotonin-RhoA/ROCK axis promotes acinar-to-ductal metaplasia in caerulein-induced chronic pancreatitis

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Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation

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Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis

L. Xia et al.

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Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells' heterogeneity

Yehuda Schlesinger et al.

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Fenglin Hu et al.

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Impaired TFEB-mediated lysosomal biogenesis promotes the development of pancreatitis in mice and is associated with human pancreatitis

Shaogui Wang et al.

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Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion

Shin Kibe et al.

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Wnt/β-catenin signalling plays diverse functions during the process of fibrotic remodelling in the exocrine pancreas

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Wnt/β-catenin signaling mediates both heart and kidney injury in type 2 cardiorenal syndrome

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Parathyroid hormone-related protein activates HSCs via hedgehog signalling during liver fibrosis development

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ANNUAL REVIEW OF BIOCHEMISTRY, VOL 88 (2019)

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Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture

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Epithelial NEMO/IKKγ limits fibrosis and promotes regeneration during pancreatitis

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Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis

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Parathyroid Hormone-Related Protein Interacts With the Transforming Growth Factor-β/Bone Morphogenetic Protein-2/Gremlin Signaling Pathway to Regulate Proinflammatory and Profibrotic Mediators in Pancreatic Acinar and Stellate Cells

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Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs

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JOURNAL OF CELL BIOLOGY (2013)

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Article Medicine, Research & Experimental

Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice

Ning Li et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

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Review Endocrinology & Metabolism

Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

Montserrat Romero et al.

JOURNAL OF DIABETES RESEARCH (2013)

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Review Physiology

Contribution of bone marrow derived cells to the pancreatic tumor microenvironment

Christopher J. Scarlett

FRONTIERS IN PHYSIOLOGY (2013)

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Review Biochemistry & Molecular Biology

Mechanisms of fibrosis: therapeutic translation for fibrotic disease

Thomas A. Wynn et al.

NATURE MEDICINE (2012)

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Article Endocrinology & Metabolism

Role of parathyroid hormone-related protein in the pro-inflammatory and pro-fibrogenic response associated with acute pancreatitis

Vandanajay Bhatia et al.

REGULATORY PEPTIDES (2012)

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Article Gastroenterology & Hepatology

Myeloid, but Not Pancreatic, RelA/p65 Is Required for Fibrosis in a Mouse Model of Chronic Pancreatitis

Matthias Treiber et al.

GASTROENTEROLOGY (2011)

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Article Gastroenterology & Hepatology

Retinoic Acid-Induced Pancreatic Stellate Cell Quiescence Reduces Paracrine Wnt-β-Catenin Signaling to Slow Tumor Progression

Fieke E. M. Froeling et al.

GASTROENTEROLOGY (2011)

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Article Gastroenterology & Hepatology

TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis

Rafaz Hoque et al.

GASTROENTEROLOGY (2011)

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Article Gastroenterology & Hepatology

Lineage Tracing Evidence for Transdifferentiation of Acinar to Duct Cells and Plasticity of Human Pancreas

Isabelle Houbracken et al.

GASTROENTEROLOGY (2011)

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Article Gastroenterology & Hepatology

Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis

Andreia V. Pinho et al.

GUT (2011)

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Article Medicine, Research & Experimental

Pancreatic ductal cells in development, regeneration, and neoplasia

Maximilian Reichert et al.

JOURNAL OF CLINICAL INVESTIGATION (2011)

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Review Immunology

Crosstalk in NF-κB signaling pathways

Andrea Oeckinghaus et al.

NATURE IMMUNOLOGY (2011)

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Article Pathology

Peroxisome Proliferator-Activated Receptor (PPAR)γ Can Inhibit Chronic Renal Allograft Damage

Eva Kiss et al.

AMERICAN JOURNAL OF PATHOLOGY (2010)

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Article Biochemistry & Molecular Biology

Albumin mediates PPAR-gamma or C/EBP-alpha-induced phenotypic changes in pancreatic stellate cells

Nayoung Kim et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2010)

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Article Gastroenterology & Hepatology

Differentiation of Pancreatic Acinar Cells to Hepatocytes Requires an Intermediate Cell Type

Sung-Yu Wu et al.

GASTROENTEROLOGY (2010)

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Article Gastroenterology & Hepatology

Corticosteroids Correct Aberrant CFTR Localization in the Duct and Regenerate Acinar Cells in Autoimmune Pancreatitis

Shigeru B. H. Ko et al.

GASTROENTEROLOGY (2010)

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Article Cell Biology

The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation

Ian Lian et al.

GENES & DEVELOPMENT (2010)

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Article Biochemistry & Molecular Biology

Identification of Epithelial to Mesenchymal Transition as a Novel Source of Fibroblasts in Intestinal Fibrosis

Sarah N. Flier et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

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Article Cell Biology

Evidence for Epithelial-Mesenchymal Transition in Adult Human Pancreatic Exocrine Cells

Marjorie Fanjul et al.

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY (2010)

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Article Multidisciplinary Sciences

Dexamethasone Treatment Induces the Reprogramming of Pancreatic Acinar Cells to Hepatocytes and Ductal Cells

Amani Al-Adsani et al.

PLOS ONE (2010)

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Article Respiratory System

Effects of PPARγ ligands on TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

Xiahui Tan et al.

RESPIRATORY RESEARCH (2010)

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Article Pathology

Rosiglitazone Abrogates Bleomycin-Induced Scleroderma and Blocks Profibrotic Responses Through Peroxisome Proliferator-Activated Receptor-γ

Minghua Wu et al.

AMERICAN JOURNAL OF PATHOLOGY (2009)

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Article Gastroenterology & Hepatology

Ras Activity in Acinar Cells Links Chronic Pancreatitis and Pancreatic Cancer

Craig D. Logsdon et al.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2009)

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Article Gastroenterology & Hepatology

Roles of Pancreatic Stellate Cells in Pancreatic Inflammation and Fibrosis

Atsushi Masamune et al.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2009)

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Article Gastroenterology & Hepatology

Pancreatic Inactivation of c-Myc Decreases Acinar Mass and Transdifferentiates Acinar Cells Into Adipocytes in Mice

Claire Bonal et al.

GASTROENTEROLOGY (2009)

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Article Gastroenterology & Hepatology

Ras Activity Levels Control the Development of Pancreatic Diseases

Baoan Ji et al.

GASTROENTEROLOGY (2009)

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Article Gastroenterology & Hepatology

Notch Signaling as Gatekeeper of Rat Acinar-to-β-Cell Conversion in Vitro

Luc Baeyens et al.

GASTROENTEROLOGY (2009)

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Review Gastroenterology & Hepatology

Epithelial-to-Mesenchymal Transitions in the Liver

Steve S. Choi et al.

HEPATOLOGY (2009)

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Article Physiology

PPAR-γ agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis

Jami E. Milam et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2008)

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Article Gastroenterology & Hepatology

Notch signaling is required for exocrine regeneration after acute pancreatitis

Jens T. Sivere et al.

GASTROENTEROLOGY (2008)

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Article Gastroenterology & Hepatology

Pancreatic stellate cells: Molecular mechanism of pancreatic fibrosis

Kyoko Shimizu

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2008)

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Editorial Material Pharmacology & Pharmacy

Reprogramming pancreatic exocrine cells to β-cells

[Anonymous]

CLINICAL PHARMACOLOGY & THERAPEUTICS (2008)

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Article Multidisciplinary Sciences

Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia

De La O. Jean-Paul et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Article Gastroenterology & Hepatology

Hypermethylation and aberrant expression of secreted fizzled-related protein genes in pancreatic cancer

Xian-Min Bu et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2008)

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Article Multidisciplinary Sciences

In vivo reprogramming of adult pancreatic exocrine cells to β-cells

Qiao Zhou et al.

NATURE (2008)

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Article Gastroenterology & Hepatology

Basic-liver, pancreas, and biliary tract

Oliver Strobel et al.

GASTROENTEROLOGY (2007)

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Article Biochemistry & Molecular Biology

Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition

Michael Zeisberg et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Article Medicine, Research & Experimental

Preexisting pancreatic to acinar cell, but not islet β cell, regeneration

Biva M. Desai et al.

JOURNAL OF CLINICAL INVESTIGATION (2007)

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Article Gastroenterology & Hepatology

Enhanced expression of interieukin-18 in serum and pancreas of patients with chronic pancreatitis

Alexander Schneider et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2006)

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Article Pathology

Fibrogenesis in alcoholic chronic pancreatitis:: the role of tissue necrosis, macrophages, myofibroblasts and cytokines

Soenke Detlefsen et al.

MODERN PATHOLOGY (2006)

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Article Developmental Biology

β-Catenin is essential for pancreatic acinar but not islet development

LC Murtaugh et al.

DEVELOPMENT (2005)

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Article Multidisciplinary Sciences

Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells

K Minami et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

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Article Developmental Biology

Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates

AL Means et al.

DEVELOPMENT (2005)

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Article Developmental Biology

Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues

KD Tremblay et al.

DEVELOPMENTAL BIOLOGY (2005)

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Article Biochemistry & Molecular Biology

Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney

M Zeisberg et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2005)

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Article Endocrinology & Metabolism

In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells

L Baeyens et al.

DIABETOLOGIA (2005)

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Article Clinical Neurology

Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis

JL Martín-Ventura et al.

STROKE (2003)

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Article Gastroenterology & Hepatology

Association of keratin 8 gene mutation with chronic pancreatitis

GM Cavestro et al.

DIGESTIVE AND LIVER DISEASE (2003)

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Article Gastroenterology & Hepatology

Up-regulation of p75 neurotrophin receptor (p75NTR) is associated with apoptosis in chronic pancreatitis

ZW Zhu et al.

DIGESTIVE DISEASES AND SCIENCES (2003)

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Review Developmental Biology

Transdifferentiation of pancreas to liver

CN Shen et al.

MECHANISMS OF DEVELOPMENT (2003)

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Article Endocrinology & Metabolism

Overexpression of parathyroid hormone-related protein inhibits pancreatic β-cell death in vivo and in vitro

A Cebrian et al.

DIABETES (2002)

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Article Cell Biology

Nestin expression in pancreatic stellate cells and angiogenic endothelial cells

J Lardon et al.

HISTOCHEMISTRY AND CELL BIOLOGY (2002)

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Review Pharmacology & Pharmacy

Parathyroid hormone-related protein and its receptors:: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets

TL Clemens et al.

BRITISH JOURNAL OF PHARMACOLOGY (2001)

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Article Cell Biology

Molecular basis of transdifferentiation of pancreas to liver

CN Shen et al.

NATURE CELL BIOLOGY (2000)

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Article Biochemistry & Molecular Biology

Suppression of NF-κB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells

H Kim et al.

FREE RADICAL BIOLOGY AND MEDICINE (2000)

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Article Pathology

Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: Study of five cases, one arising in a mediastinal teratoma

N Cingolani et al.

HUMAN PATHOLOGY (2000)

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Article Endocrinology & Metabolism

Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

I Rooman et al.

DIABETOLOGIA (2000)

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Review Medicine, General & Internal

Mechanisms of disease - The physiology of parathyroid hormone-related protein

GJ Strewler

NEW ENGLAND JOURNAL OF MEDICINE (2000)

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