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Search results for: HATH1

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#29436668   2018/02/13 To Up

Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals.

Various amino acids regulate cell growth and differentiation. In the present study, we examined the ability of HT-29 cells to differentiate into goblet cells in RPMI and DMEM which are largely different in the amounts of numerous amino acids. Most of the HT-29 cells differentiated into goblet cells downregulating the stem cell marker Lgr5 when cultured in DMEM, but remained undifferentiated in RPMI. The goblet cell differentiation in DMEM was inhibited by 1-methyl-tryptophan (1-MT), an inhibitor of indoleamine 2,3 dioxygenase-1 which is the initial enzyme in tryptophan metabolism along the kynurenine (KN) pathway, whereas tryptophan and KN induced goblet cell differentiation in RPMI. The levels of Notch1 and its activation product Notch intracytoplasmic domain in HT-29 cells were lower in DMEM than those in RPMI and were increased by 1-MT in both media. HT-29 cells grown in both media expressed β-catenin at the same level on day 2 when goblet cell differentiation was not observed. β-catenin expression, which was increased by 1-MT in both media, was decreased by KN. DMEM reduced Hes1 expression while enhancing Hath1 expression. Finally, aryl hydrocarbon receptor (AhR) activation moderately induced goblet cell differentiation. Our results suggest that KN promotes goblet cell differentiation by regulating Wnt, Notch, and AhR signals and expression of Hes1 and Hath1.
Joo-Hung Park, Jeong-Min Lee, Eun-Jin Lee, Da-Jeong Kim, Won-Bhin Hwang

2801 related Products with: Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals.

1.5 x 10^6 cells1 mg2 x 10^6 cells10 ug5 x 50 ug50 ug1.00 flask1 mg

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#28811552   2017/08/15 To Up

Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals.

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.
Bettina K Wölnerhanssen, Andrew W Moran, Galina Burdyga, Anne Christin Meyer-Gerspach, Ralph Peterli, Michael Manz, Miriam Thumshirn, Kristian Daly, Christoph Beglinger, Soraya P Shirazi-Beechey

2135 related Products with: Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals.

5 x 50 ug50 ug96 assays100 μg100ug Lyophilized2 Pieces/Box20 ug

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#27551331   // To Up

MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer.

MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC. We first knocked down (KD) β-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant β-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relative to adjacent normal tissue, with increased cytosolic/nuclear β-catenin. Luciferase assays with the complete MUC4 promoter construct p3778 showed increased MUC4 promoter luciferase activity in the absence of β-catenin (KD). Mutation of all three putative TCF/LEF sites showed that MUC4 promoter luciferase activity was increased relative to the un-mutated promoter. Interestingly, it was observed that MUC4 expressing CRC cell lines also expressed high levels of Hath1, a transcription factor repressed by both active Wnt/β-catenin and Notch signaling. The KD of β-catenin and/or treatment with a Notch γ-secretase inhibitor, Dibenzazepine (DBZ) resulted in increased Hath1 and MUC4 in LS180, HCT-8 and HCT116. Furthermore, overexpression of Hath1 in HCT-8 and LS180 caused increased MUC4 transcript and MUC4 protein. Taken together, our results indicate that the Wnt/β-catenin pathway suppresses the Notch pathway effector Hath1, resulting in reduced MUC4 in CRC.
Priya Pai, Satyanarayana Rachagani, Punita Dhawan, Yuri M Sheinin, Muzafar A Macha, Asif Khurshid Qazi, Seema Chugh, Moorthy P Ponnusamy, Kavita Mallya, Ramesh Pothuraju, Surinder K Batra

1067 related Products with: MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer.

12 Pieces/Box7 inhibitors

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#27158355   2016/02/15 To Up

DAPT mediates atoh1 expression to induce hair cell-like cells.

Hearing loss is currently an incurable degenerative disease characterized by a paucity of hair cells (HCs), which cannot be spontaneously replaced in mammals. Recent technological advancements in gene therapy and local drug delivery have shed new light for hearing loss. Atoh1, also known as Math1, Hath1, and Cath1, is a proneural basic helix-loop-helix (bHLH) transcription factor that is essential for HC differentiation. At various stages in development, Atoh1 activity is sufficient to drive HC differentiation in the cochlea. Thus, Atoh1 related gene therapy is the most promising option for HC induction. DAPT, an inhibitor of Notch signaling, enhances the expression of Atoh1 indirectly, which in turn promotes the induction of a HC fate. Here, we show that DAPT cooperates with Atoh1 to synergistically promote HC fate in ependymal cells in vitro and promote hair cell regeneration in the cultured basilar membrane (BM) which mimics the microenvironment in vivo. Taken together, our findings demonstrated that DAPT is sufficient to induce HC-like cells via enhancing of the expression of Atoh1 to inhibit the progression of HC apoptosis and to induce new HC formation.
Hongmiao Ren, Weiwei Guo, Wei Liu, Weiqiang Gao, Dinghua Xie, Tuanfang Yin, Shiming Yang, Jihao Ren

1570 related Products with: DAPT mediates atoh1 expression to induce hair cell-like cells.

One Vial: 5 X 10^6 Cells1.5 x 10^6 cells400 ug2 X 10(6) cells500 gm.cultured cells (100 ml)400 ug1.5 x 10^6 cells

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#26648003   2015/10/21 To Up

Effect of Hath1 on the proliferation and apoptosis of cutaneous squamous cell carcinoma in vitro.

Increasing evidence has demonstrated that the tumor suppressor gene Hath1 is implicated in the development and progression of tumors and is verified to be downregulated in several types of tumor. However, the roles and precise molecular mechanisms of Hath1 in cutaneous squamous cell carcinoma (SCC) remain to be elucidated. In the present study, two approaches were used to investigate the tumor‑suppressing effect of Hath1 in cutaneous SCC. Firstly, the effect of inhibiting Hath1 expression with short hairpin RNA (shRNA) on tumor growth and apoptosis was investigated. KUMA5 cells were stably transfected with a plasmid expressing Hath1 shRNA (pGenesil‑1‑Hath1). Secondly, the anti‑tumor effect of Hath1 was investigated in KUMA5 cells following transfection with pcDNA3.1‑Hath1. The mRNA and protein expression of Hath1 was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation in vitro was assessed using an MTT assay. Flow cytometry was used to detect cell apoptosis. The results demonstrated that compared with the control groups, the expression of Hath1 was significantly reduced in the KUMA5/pGenesil‑1‑Hath1 cells and markedly increased in the KUMA5/pcDNA3.1‑Hath1 cells. Cell proliferation was markedly increased in the KUMA5/pGenesil‑1‑Hath1 cells in a time‑dependent manner; however, it was markedly inhibited in the KUMA5/pcDNA3.1‑Hath1 cells. Flow cytometry revealed that apoptosis decreased in KUMA5/pGenesil‑1‑Hath1 cells and increased in KUMA5/pcDNA3.1‑Hath1 cells. Downregulation of Hath1 expression promoted the proliferation and reduced the apoptosis of KUMA5 cells. By contrast, overexpression of Hath1 inhibited proliferation and induced the apoptosis of KUMA5 cells. These findings provide possible new strategies and therapeutic targets for the treatment and diagnosis of cutaneous SCC.
Zuolin Ying, Xiaojie Li, Hong Dang, Feng Wang, Xiaoyan Xu

1303 related Products with: Effect of Hath1 on the proliferation and apoptosis of cutaneous squamous cell carcinoma in vitro.



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#25760435   2015/04/13 To Up

Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between ATOH1 Homologues.

The transcription factor atonal homolog 1 (ATOH1) has multiple homologues that are functionally conserved across species and is responsible for the generation of sensory hair cells. To evaluate potential functional differences between homologues, human and mouse ATOH1 (HATH1 and MATH-1, respectively) were nonvirally delivered to human Wharton's jelly cells (hWJCs) for the first time. Delivery of HATH1 to hWJCs demonstrated superior expression of inner ear hair cell markers and characteristics than delivery of MATH-1. Inhibition of HES1 and HES5 signaling further increased the atonal effect. Transfection of hWJCs with HATH1 DNA, HES1 siRNA, and HES5 siRNA displayed positive identification of key hair cell and support cell markers found in the cochlea, as well as a variety of cell shapes, sizes, and features not native to hair cells, suggesting the need for further examination of other cell types induced by HATH1 expression. In the first side-by-side evaluation of HATH1 and MATH-1 in human cells, substantial differences were observed, suggesting that the two atonal homologues may not be interchangeable in human cells, and artificial expression of HATH1 in hWJCs requires further study. In the future, this line of research may lead to engineered systems that would allow for evaluation of drug ototoxicity or potentially even direct therapeutic use.
Adam J Mellott, Keerthana Devarajan, Heather E Shinogle, David S Moore, Zsolt Talata, Jennifer S Laurence, M Laird Forrest, Sumihare Noji, Eiji Tanaka, Hinrich Staecker, Michael S Detamore

1635 related Products with: Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between ATOH1 Homologues.

1.00 flask 100ul1.00 flask1 mg1mg1.00 flask10 ug14 X 250 ml.1.00 flask1.00 flask

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#24611726   // To Up

Atoh1: landscape for inner ear cell regeneration.

Hearing impairment is primarily attributed to inner ear hair cell (HC) defects that subsequently lead to spiral ganglion neuron (SGN) loss. The HC loss cannot be self-repaired because of the HCs' limited capacity to regenerate in mammals. Atoh1, also known as Math1, Hath1, and Cath1, is a proneural basic helix-loop-helix (bHLH) transcription factor that played a major role in HC differentiation. Atoh1 activity at various developmental stages can sufficiently drive HC differentiation in the cochlea. Recent issues of a certain publication have identified that Atoh1 is essential for inner ear development, such as cell growth, morphogenesis, differentiation, cellular maintenance, and survival. We summarize the new findings in Atoh1 research and identify the mechanisms underlying the role of Atoh1 in HC regeneration to launch the future of Atoh1 therapy.
Ren Hongmiao, Liu Wei, Hu Bing, Ding Da Xiong, Ren Jihao

1267 related Products with: Atoh1: landscape for inner ear cell regeneration.

50 ml10 ml 5 lt0.1ml (1mg/ml)500 ml500 ml10 lt50 ml10 ml

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#23418447   2013/02/13 To Up

Bacteria regulate intestinal epithelial cell differentiation factors both in vitro and in vivo.

The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell.
Svetlana Becker, Tobias A Oelschlaeger, Andy Wullaert, Katerina Vlantis, Manolis Pasparakis, Jan Wehkamp, Eduard F Stange, Michael Gersemann

1054 related Products with: Bacteria regulate intestinal epithelial cell differentiation factors both in vitro and in vivo.

96 assays96 tests96 wells100 μg100 μg100ug Lyophilized100ug Lyophilized1.00 flask

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#23409082   2013/02/11 To Up

Differential roles of Hath1, MUC2 and P27Kip1 in relation with gamma-secretase inhibition in human colonic carcinomas: a translational study.

Hath1, a bHLH transcription factor negatively regulated by the γ-secretase-dependent Notch pathway, is required for intestinal secretory cell differentiation. Our aim was fourfold: 1) determine whether Hath1 is able to alter the phenotype of colon cancer cells that are committed to a differentiated phenotype, 2) determine whether the Hath1-dependent alteration of differentiation is coupled to a restriction of anchorage-dependent growth, 3) decipher the respective roles of three putative tumor suppressor genes Hath1, MUC2 and P27kip1 in this coupling and, 4) examine how our findings translate to primary tumors. Human colon carcinoma cell lines that differentiate along a mucin secreting (MUC2/MUC5AC) and/or enterocytic (DPPIV) lineages were maintained on inserts with or without a γ-secretase inhibitor (DBZ). Then the cells were detached and their ability to survive/proliferate in the absence of substratum was assessed. γ-secretase inhibition led to a Hath1-mediated preferential induction of MUC2 over MUC5AC, without DPPIV modification, in association with a decrease in anchorage-independent growth. While P27kip1 silencing relieved the cells from the Hath1-induced decrease of anchorage-independent growth, MUC2 silencing did not modify this parameter. Hath1 ectopic expression in the Hath1 negative enterocytic Caco2 cells led to a decreased anchorage-independent growth in a P27kip1-independent manner. In cultured primary human colon carcinomas, Hath1 was up-regulated in 7 out of 10 tumors upon DBZ treatment. Parallel MUC2 up-regulation occurred in 4 (4/7) and P27kip1 in only 2 (2/7) tumors. Interestingly, the response patterns of primary tumors to DBZ fitted with the hierarchical model of divergent signalling derived from our findings on cell lines.
Frédérique Souazé, Chantal Bou-Hanna, Christine Kandel, François Leclair, Julie Devallière, Béatrice Charreau, Stéphane Bézieau, Jean-François Mosnier, Christian L Laboisse

1942 related Products with: Differential roles of Hath1, MUC2 and P27Kip1 in relation with gamma-secretase inhibition in human colonic carcinomas: a translational study.

100 μg100 μg25mg100ug Lyophilized100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg

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#22786753   // To Up

H. pylori induces the expression of Hath1 in gastric epithelial cells via interleukin-8/STAT3 phosphorylation while suppressing Hes1.

Chronic gastritis associated with Helicobacter pylori is a leading cause of gastric intestinal metaplasia (IM), which arises from abnormal cell differentiation of the epithelium in the gastric mucosa. However, the mechanisms involved in H. pylori-mediated IM remain elusive. The aim of our study was to explore the effects and the underlying mechanisms of H. pylori on the abnormal expression of Hath1 and Sox2 and to reveal its relationship to the development of gastric IM. We found that Hath1 and Sox2 were overexpressed in gastric IM tissue. Hath1 expression was up-regulated, whereas Sox2 expression, which was independent of the CagA virulence factor, was down-regulated in gastric epithelial cells and coincided with increased IL-6 and IL-8 levels in the culture media. Stimulation with H. pylori-related cytokine IL-8, but not IL-6 or IL-1β, was induced by Hath1 expression in the gastric epithelial cells. Although IL-8 and IL-6 levels correlated with STAT3 (signal transducer and activator of transcription) phosphorylation before and after H. pylori eradication in the gastric mucosa, only the blocking of IL-8-induced STAT3 activation using AG490 or STAT3-targeting RNA interference altered Hath1 expression. Additionally, we found that H. pylori down-regulated Hes1, which is a direct downstream target gene of Notch signaling and a repressor of Hath1 expression. These findings suggest that H. pylori induced inflammation up-regulate Hath1 expression via interleukin-8/STAT3 (IL-8) phosphorylation while suppressing Hes1, which provides a novel molecular connection between a H. pylori infection and intestinal metaplasia.
Xin Zhang, Yongtao Yang, Rong Zhu, Jianying Bai, Yin Tian, Xiaohuan Li, Zhihong Peng, Yonghong He, Lei Chen, Dianchun Fang, Wensheng Chen, Quanming Zou, Xuhu Mao, Rongquan Wang

2877 related Products with: H. pylori induces the expression of Hath1 in gastric epithelial cells via interleukin-8/STAT3 phosphorylation while suppressing Hes1.

96 wells (1 kit)10 2 Pieces/Box2ug1 Set100.00 ug2ug10 96 wells (1 kit) 0.1 mg 10

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