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Pancreatic acinar cells

Li Wen, Tanveer A Javed, Dean Yimlamai, Amitava Mukherjee, Xiangwei Xiao, Sohail Z Husain
BACKGROUND AND AIMS: Pancreatitis following endoscopic retrograde cholangiopancreatography (PEP) is thought to be provoked by pancreatic ductal hypertension, via unknown mechanisms. We investigated the effects of hydrostatic pressures on the development of pancreatitis in mice. METHODS: We performed studies with Swiss Webster mice, B6129 mice (controls), and B6129 mice with disruption of the protein phosphatase 3, catalytic subunit, beta isoform gene (Cnab-/- mice)...
June 18, 2018: Gastroenterology
Marta Bombardo, Ermanno Malagola, Rong Chen, Arcangelo Carta, Gitta M Seleznik, Andrew P Hills, Rolf Graf, Sabrina Sonda
Adult pancreatic acinar cells have the ability to re-enter the cell cycle and proliferate upon injury or tissue loss. Despite this mitotic ability, the extent of acinar proliferation is often limited and unable to completely regenerate the injured tissue or restore the initial volume of the organ, thus leading to pancreatic dysfunction. Identifying molecular determinants of enhanced proliferation is critical to overcome this issue. In this study, we discovered that Murphy Roths Large (MRL/MpJ) mice can be exploited to identify molecular effectors promoting acinar proliferation upon injury, with the ultimate goal to develop therapeutic regimens to boost pancreatic regeneration...
June 20, 2018: Scientific Reports
Shira Anzi, Miri Stolovich-Rain, Agnes Klochendler, Ori Fridlich, Aharon Helman, Avital Paz-Sonnenfeld, Nili Avni-Magen, Elizabeth Kaufman, Miriam B Ginzberg, Daniel Snider, Saikat Ray, Michael Brecht, Melissa M Holmes, Karen Meir, Aaron Avivi, Imad Shams, Asaf Berkowitz, A M James Shapiro, Benjamin Glaser, Shmuel Ben-Sasson, Ran Kafri, Yuval Dor
Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia...
June 18, 2018: Developmental Cell
Matthew D Smith, Simon Wilkinson
The importance of selective macroautophagy/autophagy in cellular health is increasingly evident. The selective degradation of portions of the endoplasmic reticulum (ER), or reticulophagy, is an emerging example but requires further mechanistic detail and broad evidence of physiological relevance. In a recent study, we identified CCPG1, an ER-resident transmembrane protein that can bind to Atg8-family proteins and, independently and discretely, to RB1CC1/FIP200. Both of these interactions are required to facilitate CCPG1's function as a reticulophagy cargo receptor...
June 19, 2018: Autophagy
Xiaozheng Yu, Chunyun Li, Hechao Song, Xueyan Wang, Yinan Guo, Lijian Cui, Xiaoya Liu, Cheng Chi, Ruixia Liu, Chenghong Yin
OBJECTIVES: The aim of this study was to investigate the effects of emodin on attenuating autophagy response in acute pancreatitis (AP) models. METHODS: Acute pancreatitis was induced in Wistar rats by injecting 3% sodium taurocholate into the biliopancreatic duct. Emodin (40 mg/kg per day) was then given intragastrically, administrated 2 hours after AP induction. Rats were killed 24 hours after AP induction. The pancreatic injury was assessed using biochemical and histological approaches...
June 16, 2018: Pancreas
Marissa A Scavuzzo, Jessica Teaw, Diane Yang, Malgorzata Borowiak
The pancreas is a complex organ composed of many different cell types that work together to regulate blood glucose homeostasis and digestion. These cell types include enzyme-secreting acinar cells, an arborized ductal system responsible for the transportation of enzymes to the gut, and hormone-producing endocrine cells. Endocrine beta-cells are the sole cell type in the body that produce insulin to lower blood glucose levels. Diabetes, a disease characterized by a loss or the dysfunction of beta-cells, is reaching epidemic proportions...
June 2, 2018: Journal of Visualized Experiments: JoVE
Jordan Orr, Robert Lockwood, Jordan Roberts, Chanjuan Shi, Patrick Yachimski
No abstract text is available yet for this article.
June 12, 2018: Gastrointestinal Endoscopy
Shuang Peng, Julia V Gerasimenko, Tetyana M Tsugorka, Oleksiy Gryshchenko, Sujith Samarasinghe, Ole H Petersen, Oleg V Gerasimenko
Acute pancreatitis (AP), a human disease in which the pancreas digests itself, has substantial mortality with no specific therapy. The major causes of AP are alcohol abuse and gallstone complications, but it also occurs as an important side effect of the standard Asparaginase-based therapy for childhood acute lymphoblastic leukaemia. Previous investigations into the mechanisms underlying pancreatic acinar cell death induced by alcohol metabolites, bile acids or Asparaginase indicated that loss of intracellular ATP generation is a significant factor...
June 12, 2018: Journal of Clinical Investigation
Yojiro Sakuma, Yuzo Kodama, Takaaki Eguchi, Norimitsu Uza, Yoshihisa Tsuji, Masahiro Shiokawa, Takahisa Maruno, Katsutoshi Kuriyama, Yoshihiro Nishikawa, Yuki Yamauchi, Motoyuki Tsuda, Tatsuki Ueda, Tomoaki Matsumori, Toshihiro Morita, Teruko Tomono, Nobuyuki Kakiuchi, Atsushi Mima, Yuko Sogabe, Saiko Marui, Takeshi Kuwada, Akihiko Okada, Tomohiro Watanabe, Hiroshi Nakase, Tsutomu Chiba, Hiroshi Seno
Severe acute pancreatitis is a lethal inflammatory disease frequently accompanied by pancreatic necrosis. We aimed to identify a key regulator in the development of pancreatic necrosis. A cytokine/chemokine array using sera from patients with acute pancreatitis (AP) revealed that serum CXCL16 levels were elevated according to the severity of pancreatitis. In a mouse model of AP, Cxcl16 expression was induced in pancreatic acini in the late phase with the development of pancreatic necrosis. Cxcl16-/- mice revealed similar sensitivity as wild-type (WT) mice to the onset of pancreatitis, but better resisted development of acinar cell necrosis with attenuated neutrophil infiltration...
June 11, 2018: Scientific Reports
Kohei Yasunaga, Tetsuhide Ito, Masami Miki, Keijiro Ueda, Takashi Fujiyama, Yuichi Tachibana, Nao Fujimori, Ken Kawabe, Yoshihiro Ogawa
Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis...
2018: BioMed Research International
Marta Bombardo, Rong Chen, Ermanno Malagola, Enrica Saponara, Andrew P Hills, Rolf Graf, Sabrina Sonda
Pancreatic fibrosis is the hallmark of chronic pancreatitis, a highly debilitating disease for which there is currently no cure. The key event at the basis of pancreatic fibrosis is the deposition of extracellular matrix proteins by activated pancreatic stellate cells (PSC). Transforming growth factor β (TGFβ) is a potent pro-fibrotic factor in the pancreas as it promotes the activation of PSC, thus pharmacologic interventions that effectively reduce TGFβ expression harbor considerable therapeutic potential in the treatment of chronic pancreatitis...
June 7, 2018: Molecular Pharmacology
Dan Du, Linbo Yao, Rui Zhang, Na Shi, Yan Shen, Xinmin Yang, Xiaoying Zhang, Tao Jin, Tingting Liu, Liqiang Hu, Zhihua Xing, David N Criddle, Qing Xia, Wei Huang, Robert Sutton
ETHNOPHARMACOLOGICAL RELEVANCE: Oxidative stress is a prominent feature of clinical acute pancreatitis (AP). Coreopsis tinctoria has been used traditionally to treat pancreas disorders like diabetes mellitus in China and Portugal and its flavonoid-rich fraction contain the main phytochemicals that have antioxidant and anti-inflammatory activities. AIM OF THE STUDY: To investigate the effects of flavonoids isolated from C. tinctoria on experimental AP and explore the potential mechanism...
June 2, 2018: Journal of Ethnopharmacology
A A Alahmari, B Sreekumar, V Patel, M Ashat, M Alexandre, A K Uduman, E O Akinbiyi, A Ceplenski, C A Shugrue, T R Kolodecik, N Tashkandi, S W Messenger, G E Groblewski, F S Gorelick, E C Thrower
Clinical studies have shown that cigarette smoking is a dose-dependent and independent risk factor for acute pancreatitis. Cigarette smoke contains nicotine which can be converted to the potent receptor ligand and toxin, NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Previously, we have shown that NNK induces premature activation of pancreatic zymogens in rats, an initiating event in pancreatitis, and this activation is prevented by pharmacologic inhibition of nicotinic acetylcholine receptors (nAChR)...
2018: PloS One
Hong Ning Jiang, Yuan Li, Wen Yi Jiang, Zong Jie Cui
Plasma membrane-delimited generation of singlet oxygen by photodynamic action with photosensitizer sulfonated aluminum phthalocyanine (SALPC) activates cholecystokinin 1 receptor (CCK1R) in pancreatic acini. Whether CCK1R retains such photooxidative singlet oxygen activation properties in other environments is not known. Genetically encoded protein photosensitizers KillerRed or mini singlet oxygen generator (miniSOG) were expressed in pancreatic acinar tumor cell line AR4-2J, CCK1R, KillerRed or miniSOG were expressed in HEK293 or CHO-K1 cells...
2018: Frontiers in Physiology
Baiqiang Li, Na Yang, Chuling Li, Chuwei Li, Kun Gao, Xiaochun Xie, Xiaowu Dong, Jing Yang, Qi Yang, Zhihui Tong, Guotao Lu, Weiqin Li
Bile acids receptor TGR5 and its agonist INT-777, which has been found to be involved in the NLRP3 inflammasome pathway, play an important role in inflammatory diseases. However, the role of INT-777 in acute pancreatitis (AP) has not been reported. In this present study, we found that TGR5 was expressed in pancreatic tissue and increased after AP onset induced by caerulein and further evaluated the impact of INT-777 on the severity of AP. The results showed that INT-777 could reduce the severity of AP in mice, which was manifested as decreased pancreatic tissue damage as well as the decrease of serum enzymes (amylase and lipase), pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and the expression of necrosis related proteins (RIP3 and p-MLKL)...
May 30, 2018: Biochemical and Biophysical Research Communications
Hirofumi Shibata, Shingo Komura, Yosuke Yamada, Nao Sankoda, Akito Tanaka, Tomoyo Ukai, Mio Kabata, Satoko Sakurai, Bunya Kuze, Knut Woltjen, Hironori Haga, Yatsuji Ito, Yoshiya Kawaguchi, Takuya Yamamoto, Yasuhiro Yamada
The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We show that the transient expression of reprogramming factors (1-3 days) in pancreatic acinar cells results in the transient repression of acinar cell enhancers, which are similarly observed in pancreatitis. We next demonstrate that Kras and p53 mutations are insufficient to induce ERK signaling in the pancreas. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce the robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma...
May 25, 2018: Nature Communications
Kozo Ikuta, Akihisa Fukuda, Satoshi Ogawa, Kenji Masuo, Norihiro Goto, Yukiko Hiramatsu, Motoyuki Tsuda, Yoshito Kimura, Yoshihide Matsumoto, Yuto Kimura, Takahisa Maruno, Keitaro Kanda, Kiyoto Nishi, Kyoichi Takaori, Shinji Uemoto, Shigeo Takaishi, Tsutomu Chiba, Eiichiro Nishi, Hiroshi Seno
OBJECTIVE: Nardilysin (NRDC), a zinc peptidase, exhibits multiple localisation-dependent functions including as an enhancer of ectodomain shedding in the extracellular space and a transcriptional coregulator in the nucleus. In this study, we investigated its functional role in exocrine pancreatic development, homeostasis and the formation of pancreatic ductal adenocarcinoma (PDA). DESIGN: We analysed Ptf1a-Cre; Nrdcflox/flox mice to investigate the impact of Nrdc deletion...
May 24, 2018: Gut
Lei Zhang, Martin H Bluth, Amarpreet Bhalla
Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations...
June 2018: Clinics in Laboratory Medicine
Oronzo Brunetti, Giuseppe Aprile, Paolo Marchetti, Enrico Vasile, Andrea Casadei Gardini, Mario Scartozzi, Sandro Barni, Sara Delfanti, Fernando De Vita, Francesco Di Costanzo, Michele Milella, Chiara Alessandra Cella, Rossana Berardi, Ivana Cataldo, Aldo Scarpa, Debora Basile, Federica Mazzuca, Giusi Graziano, Antonella Argentiero, Daniele Santini, Michele Reni, Stefano Cascinu, Nicola Silvestris
OBJECTIVES: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? METHODS: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival...
May 15, 2018: Pancreas
Xin Chen, Bin Zhu
BACKGROUND Steroid receptor coactivator-interacting protein (SIP) inhibits the activation of nuclear factor-kappa B (NF-κB) by interacting with p65. The occurrence of acute pancreatitis (AP) is closely associated with pro-inflammatory response. The present study aimed to investigate the role of SIP on myocardial injury caused by AP. MATERIAL AND METHODS Rat pancreatic acinar tumor cell line AR42J cells were treated with caerulein to establish AP cell models. The levels of TNF-α, IL-6, cTnI, CK-MB, and LDH1 were detected by ELISA assay...
May 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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