Theresia Reding Graf - Academia.edu (original) (raw)

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Papers by Theresia Reding Graf

Research paper thumbnail of Amelioration of Murine Autoimmune Pancreatitis by Targeted LTβR Inhibition and Anti-CD20 Treatment

Research paper thumbnail of Response of routine inflammatory biomarkers and novel Pancreatic Stone Protein to inhalation injury and its interference with sepsis detection in severely burned patients

Research paper thumbnail of Diagnostic Value of Pancreatic Stone Protein in comparison to White Cell Count and C-Reactive Protein in the Diagnosis of Acute Appendicitis – A Prospective MulticenterDiagnostic Accuracy Trial

Research paper thumbnail of Akt1 signalling supports acinar proliferation and limits acinar‐to‐ductal metaplasia formation upon induction of acute pancreatitis

Research paper thumbnail of Gastrokine 2 delays the development of pre-malignant PanIN lesions

Research paper thumbnail of Tumor suppressive mechanisms of Gastrokine 1 in pancreatic carcinogenesis

Research paper thumbnail of Acinar Akt1 in pancreatic acinar cells supports proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

Research paper thumbnail of Identification of Gastrokine, a gastric tumor suppressor protein, in pancreatic carcinogenesis

Research paper thumbnail of The contribution of Lymphotoxin from PanINs to pancreatic tumor development

Research paper thumbnail of The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII

Research paper thumbnail of Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar-to-ductal metaplasia

British Journal of Pharmacology

Research paper thumbnail of Development of autoimmune pancreatitis is independent of CDKN1A/p21-mediated pancreatic inflammation

Gut, Sep 3, 2017

Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are characterised by different inflam... more Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are characterised by different inflammatory processes. If pancreatic inflammation is a prerequisite for autoimmunity is still unclear. AIP is considered mostly a T cell-mediated disease; however, in induction of CP, macrophages play a pivotal role. p21-a member of cyclin-dependent kinase inhibitors-can influence inflammatory processes, in particular can regulate T cell activation and promote macrophage development. We therefore examined the role of p21-mediated inflammation in AIP. We intercrossed lymphotoxin (LT) overexpressing mice (Tg(Ela1-LTa,b))-a model to study AIP development-with p21-deficient mice. Furthermore, we characterised p21 expression in human AIP and non-AIP specimens. p21 deficiency in LT mice (LTp21(-/-)) prevented early pancreatic injury and reduced inflammation. In acinar cells, diminished proliferation and abrogated activation of non-canonical nuclear factor kappa-light-chain-enhancer of activated B c...

Research paper thumbnail of Absence of p21 attenuates pancreatic inflammation but does not affect the development of autoimmune pancreatitis

Research paper thumbnail of A heterologous hormone response element enhances expression of rat beta-casein promoter-driven chloramphenicol acetyltransferase fusion genes in the mammary gland of transgenic mice

Molecular Endocrinology, Nov 1, 1991

Research paper thumbnail of Inactivation of TGF-β receptor II signaling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis

The Journal of Pathology, 2015

Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is c... more Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer.

Research paper thumbnail of Inactivation of TGF-β receptor II signalling in pancreatic epithelial cells promotes acinar cell replication and acinar-to-ductal metaplasia formation during pancreatitis

Research paper thumbnail of Effects of p21 deficiency on murine autoimmune pancreatitis

Research paper thumbnail of Thyroid hormone T3 promotes acinar cells proliferation during pancreatitis

Research paper thumbnail of Serotonin transporter inhibition prevents Rac1-dependent cytoskeletal remodeling and reduces pancreatic acinar-to-ductal metaplasia formation

Research paper thumbnail of Diet protein content influences L-glutamate metabolism and transport in the exocrine pancreas and intestine

Research paper thumbnail of Amelioration of Murine Autoimmune Pancreatitis by Targeted LTβR Inhibition and Anti-CD20 Treatment

Research paper thumbnail of Response of routine inflammatory biomarkers and novel Pancreatic Stone Protein to inhalation injury and its interference with sepsis detection in severely burned patients

Research paper thumbnail of Diagnostic Value of Pancreatic Stone Protein in comparison to White Cell Count and C-Reactive Protein in the Diagnosis of Acute Appendicitis – A Prospective MulticenterDiagnostic Accuracy Trial

Research paper thumbnail of Akt1 signalling supports acinar proliferation and limits acinar‐to‐ductal metaplasia formation upon induction of acute pancreatitis

Research paper thumbnail of Gastrokine 2 delays the development of pre-malignant PanIN lesions

Research paper thumbnail of Tumor suppressive mechanisms of Gastrokine 1 in pancreatic carcinogenesis

Research paper thumbnail of Acinar Akt1 in pancreatic acinar cells supports proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis

Research paper thumbnail of Identification of Gastrokine, a gastric tumor suppressor protein, in pancreatic carcinogenesis

Research paper thumbnail of The contribution of Lymphotoxin from PanINs to pancreatic tumor development

Research paper thumbnail of The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII

Research paper thumbnail of Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar-to-ductal metaplasia

British Journal of Pharmacology

Research paper thumbnail of Development of autoimmune pancreatitis is independent of CDKN1A/p21-mediated pancreatic inflammation

Gut, Sep 3, 2017

Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are characterised by different inflam... more Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are characterised by different inflammatory processes. If pancreatic inflammation is a prerequisite for autoimmunity is still unclear. AIP is considered mostly a T cell-mediated disease; however, in induction of CP, macrophages play a pivotal role. p21-a member of cyclin-dependent kinase inhibitors-can influence inflammatory processes, in particular can regulate T cell activation and promote macrophage development. We therefore examined the role of p21-mediated inflammation in AIP. We intercrossed lymphotoxin (LT) overexpressing mice (Tg(Ela1-LTa,b))-a model to study AIP development-with p21-deficient mice. Furthermore, we characterised p21 expression in human AIP and non-AIP specimens. p21 deficiency in LT mice (LTp21(-/-)) prevented early pancreatic injury and reduced inflammation. In acinar cells, diminished proliferation and abrogated activation of non-canonical nuclear factor kappa-light-chain-enhancer of activated B c...

Research paper thumbnail of Absence of p21 attenuates pancreatic inflammation but does not affect the development of autoimmune pancreatitis

Research paper thumbnail of A heterologous hormone response element enhances expression of rat beta-casein promoter-driven chloramphenicol acetyltransferase fusion genes in the mammary gland of transgenic mice

Molecular Endocrinology, Nov 1, 1991

Research paper thumbnail of Inactivation of TGF-β receptor II signaling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis

The Journal of Pathology, 2015

Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is c... more Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer.

Research paper thumbnail of Inactivation of TGF-β receptor II signalling in pancreatic epithelial cells promotes acinar cell replication and acinar-to-ductal metaplasia formation during pancreatitis

Research paper thumbnail of Effects of p21 deficiency on murine autoimmune pancreatitis

Research paper thumbnail of Thyroid hormone T3 promotes acinar cells proliferation during pancreatitis

Research paper thumbnail of Serotonin transporter inhibition prevents Rac1-dependent cytoskeletal remodeling and reduces pancreatic acinar-to-ductal metaplasia formation

Research paper thumbnail of Diet protein content influences L-glutamate metabolism and transport in the exocrine pancreas and intestine

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