Hyaluronic Acid Synthase-2 (HAS2) overexpression and deficiency effect on hepatic stellate cells
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PROVIDER: PRJNA427766 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of hepatic stellate cells (HSCs) isoltaed from ASMA-HAS2 transgenic and HSC-specific Has2 knockout mice. HAS2 synthesized hyaluronic acid, one of major extracellular matrix. Results provide insight into the role of HAS2 in hepatic stellate cells.
2020-01-01 | GSE108593 | GEO
Project description:Analysis of hepatic stellate cells isoltaed from wild-type, TLR4-/-, and CD44-/- mice. TLR4 and CD44 are major hyaluronic acid receptors. Results provide insight into the effects of TLR4 and CD44 loss in hepatic stellate cells.
2020-01-01 | GSE109200 | GEO
Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2) which can generate high molecular weight hyaluronan (HMW-HA). Although we previously reported that HAS2 is a novel candidate gene for susceptibility to adult asthma., little is known about whether HAS2 dysfunction affect eosinophilic airway inflammation. Objective: We therefore hypothesized that attenuation of HAS2 will enhance eosinophilic airway inflammation. Methods: C57BL/6 wild type (WT) mice, Has2 heterozygous deficient (Has2+/−) mice were used in eosinophilic airway inflammation model which induced by ovalbumin (OVA). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect Has2 and HA binding protein mRNA expression levels. Lung tissue and lavage fluid (BALF) were analyzed for inflammation and various cytokines and chemokines. Airway resistance was measured using forced oscillation technique. gene expression analyses were also performed to elucidate further pathogenesis. Results: The expression levels of Has2 mRNA was significantly decreased in OVA stimulated Has2+/− (Has2+/−-OVA) mice. Has2+/−-OVA mice also displayed significant reduce of CD44, and TGF-beta1 mRNA expression. BALF eosinophil number, levels of various Th2 cytokines and chemokines in BALF, and airway responsiveness were significantly increased in Has2+/−-OVA mice compared with similarly treated WT mice. ILK Signaling and PKA signaling were downregulated significantly more in Has2+/−-OVA mice compared with similarly treated WT mice. Conclusions: Has2 dysfunction induce more intense allergic eosinophilic airway inflammation and increase of airway hyper responsiveness with impairment of HAS2-CD44-TGF-beta signaling. Modulating HAS2 signaling might provide novel therapeutic targets for intractable bronchial asthma patients.
2022-04-04 | GSE148161 | GEO
Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2), which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified HAS2 as a candidate gene for susceptibility to adult asthma. However, little is known if HAS2 dysfunction affects airway remodeling and steroid insensivity. In this study, we clarified the dysfunction of Has2 triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. Methods: Ovalbumin (OVA) was used to induce eosinophilic airway inflammation and airway remodeling in Has2 heterozygous deficient (Has2+/−) mice and their wild-type (WT) littermates. Lung tissue histology, bronchoalveolar lavage fluid cell counting, quantitative PCR, HA size analysis, multiplex cytokines and chemokines analysis, RNA sequencing, anti IL-17 neutralization experiment were performed. Results: After chronic OVA stimulation, Has2+/− (Has2+/--OVA) mice showed significant decrease of Has2 mRNA expression levels, HMW-HA, HA-binding protein, and TGF-β. Has2+/--OVA mice demonstrated increased eosinophilic airway inflammation, goblet cell hyperplasia, and IL-17 levels. RNA sequencing demonstrated downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in Has2+/--OVA mice. Combined treatment with anti IL-17 antibody and dexamethasone reduce steroid insensitivity in Has2+/--OVA mice Conclusions: Has2 attenuation worsen eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. This severe intractable phenotype might be induced by impairment of TGF-β signaling and ER stress response related signaling. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling, and could potentially be exploited for therapeutic benefit to asthma patients.
2022-01-26 | GSE181966 | GEO
Project description:Hepatic fibrosis remains a significant clinical challenge due to ineffective treatments. 4-methylumbelliferone (4MU), a hyaluronic acid (HA) synthesis inhibitor, has proven safe in phase one clinical trials. In this study, we aimed to ameliorate liver fibrosis by inhibiting HA synthesis. We compared two groups of mice with CCl4-induced fibrosis, treated with 4-methylumbelliferone (4MU) and hyaluronan synthase 2 (HAS2) targeting siRNA (siHAS2). The administration of 4MU and siHAS2 significantly reduced collagen and HA deposition, as well as biochemical markers of hepatic damage induced by repeated CCl4 injections. The transcriptomic analysis revealed converging pathways associated with downstream HA signalling. 4MU- and siHAS2-treated fibrotic livers shared 405 upregulated and 628 downregulated genes. These genes were associated with xenobiotic and cholesterol metabolism, mitosis, endoplasmic reticulum stress, RNA processing, and myeloid cell migration. The functional annotation of differentially expressed genes (DEGs) in siHAS2-treated mice revealed attenuation of extracellular matrix-associated pathways. In comparison, in the 4MU-treated group, DEGs were related to lipid and bile metabolism pathways and cell cycle. These findings confirm that HAS2 is an important pharmacological target for suppressing hepatic fibrosis using siRNA.
2023-08-30 | GSE241894 | GEO
Project description:Early during culture of primary mouse HSCs gene expression changes. These expression alterations can be affected by treating cells with histone deacetylase inhibitor, valproic acid Primary mouse Hepatic stellate cells were cultured for short periods of time (4-16-64h) in presence or absence of valproic acid. Gene expression analysis (mouse Gene 1.0 ST arrays according to manufacturerM-bM-^@M-^Ys manual 701880Rev4 (Affymetrix, Santa Clara, CA)), in vitro stellate cell activation and inhibition of the activation by valproic acid treatment.
2014-01-01 | E-GEOD-51882 | biostudies-arrayexpress
Project description:Loss of Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) drives bladder cancer growth. Low AGL expression predicts poor patient outcome. Currently no specific therapeutically tractable targets/pathways exist that could be used to treat patients with low AGL expressing bladder tumors. To address this issue we carried out a transcriptome analysis in human bladder cancer cells with and without AGL expression to identify pro-tumorigenic pathways upregulated with AGL loss. We identified and validated that hyaluronic acid (HA) synthase 2 (HAS2) expression and subsequent HA synthesis is upregulated with AGL loss. We validated that HAS2 and consequent HA synthesis drive tumor growth and that genetic and pharmacologic inhibition of these respectively is a viable therapeutic option in xenograft models. We further established that bladder cancer patients with low AGL expression and high HAS2 expression have poor outcome. Together, this data provide preclinical evidence for personalized targeting of HAS2/HA signaling in patients with low AGL expressing tumors.
2015-09-26 | GSE73456 | GEO
Project description:Gene expression of mouse hepatic stellate cells was characterized under the following conditions: Quiescent (isolated from normal mouse liver) and reverted (isolated from mouse liver treated with 4 injections of carbontetrachloride followed by 45 day rest period) Affymetrix Mouse 1.0ST gene expression measurements were used to characterize the transcriptomic basis in quiescent hepatic stellate cells, isolated from normal liver, and reverted hepatic stellate cells, isolated from liver treated with 4 injections of CCl4 followed by a 45 day rest period. Gene expression of mouse hepatic stellate cells was characterized under the following conditions: A. Quiescent control hepatic stellate cells (n=4). B. Reverted hepatic stellate cells (n=4).
2014-05-05 | E-GEOD-38648 | biostudies-arrayexpress
Project description:RNA sequencing of LX2 cell line (a human hepatic stellate cell line). METTL3 overexpression or downreguation were achieved by lenti-virus transduction.
2022-07-13 | GSE207909 | GEO
Project description:TLR4 or CD44 deficiency effect on hepatic stellate cells
| PRJNA430098 | ENA