346-LB: The Role of STAT3 Signaling toward a-to-ß Reprogramming within the Adult Pancreas

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 346-LB
Author(s):  
YUKA WAKABAYASHI ◽  
TAKESHI MIYATSUKA ◽  
LUKA SUZUKI ◽  
MIWA HIMURO ◽  
TAKEHIRO KATAHIRA ◽  
...  
Keyword(s):  
Stat3 Signaling

scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

scholarly journals The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shaohui Zong ◽  
Gaofeng Zeng ◽  
Ye Fang ◽  
Jinzhen Peng ◽  
Yong Tao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Hind Limb ◽  
Rating Scale ◽  
Serum Levels ◽  
Spinal Cord Tissue ◽  
Expression Levels ◽  
Stat3 Signaling ◽  
Cord Injury ◽  
Disease Stages

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

Obesity and inflammation: colorectal cancer engines

2021 ◽  
Vol 14 ◽  
Author(s):  
Lara J. Bou Malhab ◽  
Wael M. Abdel-Rahman
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Obese Patients ◽  
Epigenetic Alterations ◽  
Molecular Alterations ◽  
Stat3 Signaling ◽  
Therapeutic Choice ◽  
Prevalence Of Obesity ◽  
Inhibitory Molecules

: The prevalence of obesity continues to increase to the extent that it became a worldwide pandemic. An accumulating body of evidence has associated obesity with the development of different types of cancer, including colorectal cancer, which is a notorious disease with a high mortality rate. At the molecular level, colorectal cancer is a heterogenous disease characterized by a myriad of genetic and epigenetic alterations associated with various forms of genomic instability (detailed in Supplementary Materials). Recently, the microenvironment has emerged as a major factor in carcinogenesis. Our aim is to define the different molecular alterations leading to the development of colorectal cancer in obese patients with a focus on the role of the microenvironment in carcinogenesis. We also highlight all existent molecules in clinical trials that target the activated pathways in obesity-associated colorectal cancer, whether used as single treatments or in combination. Obesity predisposes to colorectal cancer via creating a state of chronic inflammation with dysregulated adipokines, inflammatory mediators, and other factors such as immune cell infiltration. A unifying theme in obesity-mediated colorectal cancer is the activation of the PI3K/AKT, mTOR/MAPK, and STAT3 signaling pathways. Different inhibitory molecules towards these pathways exist, increasing the therapeutic choice of obesity-associated colon cancer. However, obese patients are more likely to suffer from chemotherapy overdosing. Preventing obesity through maintaining a healthy and active lifestyle remains to be the best remedy.

scholarly journals Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Lakshana Sreenivasan ◽  
Hui Wang ◽  
Shyong Quin Yap ◽  
Pascal Leclair ◽  
Anthony Tam ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
Acquired Drug Resistance ◽  
Stat3 Signaling ◽  
Therapeutic Benefits ◽  
Signaling Axis ◽  
Neuronal Precursors ◽  
Cranial Fossa ◽  
Group 3

AbstractMedulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.

scholarly journals The Role of Curcumin in Cancer Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1086
Author(s):  
Vasiliki Zoi ◽  
Vasiliki Galani ◽  
Georgios D. Lianos ◽  
Spyridon Voulgaris ◽  
Athanasios P. Kyritsis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Curcuma Longa ◽  
Immune Modulators ◽  
Anticancer Properties ◽  
Stat3 Signaling ◽  
Anticancer Effects ◽  
Transcription 3 ◽  
Light Chain Enhancer

Curcumin is a polyphenol extracted from the rhizomes of the turmeric plant, Curcuma longa which has anti-inflammatory, and anticancer properties. Chronic inflammation is associated with the development of cancer. Curcumin acts on the regulation of various immune modulators, including cytokines, cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which partly explains its anticancer effects. It also takes part in the downregulation of growth factors, protein kinases, oncogenic molecules and various signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) signaling. Clinical trials of curcumin have been completed or are ongoing for various types of cancer. This review presents the molecular mechanisms of curcumin in different types of cancer and the evidence from the most recent clinical trials.

Role of JAK/STAT3 Signaling in Functional Stimulation of Mesenchymal Progenitor Cells with Alkaloid Songorine

2018 ◽  
Vol 165 (5) ◽  
pp. 665-668 ◽  
Author(s):  
G. N. Zyuz’kov ◽  
E. V. Udut ◽  
L. A. Miroshnichenko ◽  
T. Yu. Polyakova ◽  
E. V. Simanina ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Mesenchymal Progenitor Cells ◽  
Stat3 Signaling ◽  
Functional Stimulation ◽  
Stimulation Of

Abstract 3474: Cardiac -Specific SOCS3 Dificient Mice Shows Resistance to Lipopolysaccharide-Induced Cardiac Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Futamata Nobuyoshi ◽  
Hldeo Yasukawa ◽  
Toyoharu Ohba ◽  
Kazutoshi Mawatari ◽  
Daisuke Fukui ◽  
...  
Keyword(s):  
Western Blot ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Left Ventricular Ejection ◽  
Cytokine Signaling ◽  
Rt Pcr ◽  
Lv Dysfunction ◽  
Stat3 Signaling ◽  
Cardiomyocyte Survival

Background : Lypopolysaccharide (LPS)-induced left ventricular (LV) dysfunction is a well-established model for sepsis-induced acute heart failure. STAT3 signaling in the heart has been shown to promote cardiomyocyte survival during LPS-induced LV dysfunction. Little is known, however, about the role of negative regulation of STAT3 signaling during LPS-induced LV dysfunction. Suppressor of cytokine signaling 3 (SOCS3) is an intrinsic negative regulator of gp130 cytokine-induced STAT3 signaling that plays an important role in cardiomyocyte survival. In this study, we determined whether STAT3 signaling and its negative regulator SOCS3 would play a role in LPS-induced LV dysfunction. Methods and Results : We examined the activation of STAT3 and inductions of gp130 cytokines and SOCS3 in the wild-type (WT) mice hearts after LPS injection by western blot and real-time PCR (RT-PCR). RT-PCR revealed that gp130 cytokines were markedly increased after AMI. Western blot revealed that STAT3 was markedly phosphorylated and SOCS3 was induced in WT mice hearts after LPS injection. To investigate the role of STAT3 signaling and SOCS3 in LPS-induced LV dysfunction, we generated cardiac-specific SOCS3 knockout mice (SOCS3-CKO). Left ventricular ejection fraction (LVEF) of SOCS3-CKO mice was similar to that of WT mice at baseline (64.2 ± 6.1 vs. 62.4 ± 4.4%). LPS (30mg/kg) elicited a significant and robust reduction of LVEF in both SOCS3-CKO mice and WT mice 3 hr after LPS injection (18 ± 4.5 vs. 16 ± 5.2%, p <0.01). LVEF in WT mice was further reduced 6 hr after LPS injection. On the other hand, interestingly, LVEF was restored to the baseline in SOCS3-CKO mice 6 hr after LPS injection (10.4 ± 3.9 vs. 62.2 ± 8.1%, p <0.01). Also the duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Furthermore, SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection ( p <0.01). Conclusion : Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice, possibly by augmenting the STAT3-mediated gp130 cytokine signaling.

Role of leptin/STAT3 signaling and RIP-kinases in fucoxanthin influences on mice exposed to LPS and gamma radiation

Toxin Reviews ◽  
2021 ◽  
pp. 1-22
Author(s):  
Mohamed K. Abdel-Rafei ◽  
Noura M. Thabet ◽  
Ghada El Tawel ◽  
Nermeen M. El Bakary ◽  
Neama M. El Fatih ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Stat3 Signaling

scholarly journals Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10

2019 ◽  
Vol 216 (2) ◽  
pp. 337-349 ◽  
Author(s):  
Peng Xiao ◽  
Huilun Zhang ◽  
Yu Zhang ◽  
Mingzhu Zheng ◽  
Rongbei Liu ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Blood Monocytes ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Further Development

Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.

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