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Hydrocortisone and Triiodothyronine Regulate Hyaluronate Synthesis in a Tissue–Engineered Human Dermal Equivalent through Independent Pathways

ABSTRACT: Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in a tissue engineered human dermal matrix.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56616 | GEO | 2015/04/08

SECONDARY ACCESSION(S): PRJNA244086

REPOSITORIES: GEO

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Hydrocortisone and Triiodothyronine Regulate Hyaluronate Synthesis in a Tissue–Engineered Human Dermal Equivalent through Independent Pathways

Project description:Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in a tissue engineered human dermal matrix. RNA preparations were sent to CFG Microarray Core (E). Three replicate samples from each condition were used in the study. The RNA was amplified, labeled, and hybridized to the GLYCOv4 microarrays.

2015-04-08 | E-GEOD-56616 | biostudies-arrayexpress

Impact of hyaluronic acid on cutaneous T-cell lymphoma microenvironment: A novel anti-tumor mechanism of bexarotene

Project description:Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin lymphoma that primarily affects the skin rich in hyaluronic acid（HA）. HA composes extracellular matrix in the dermis, which likely affects the development of CTCL but is poorly understood. Here, we show that low molecular weight HA (LMWHA) possibly exacerbates CTCL in mouse and human specimens, and bexarotene already being used in CTCL treatment can decrease HA production. Patients’ serum and skin sections showed higher HA expression than healthy controls. HA extracted from the skin of mice inoculated with tumors showed an increase in LMWHA. LMWHA increased lymphoma cell proliferation in vitro and accelerated tumor formation in mice in vivo. LMWHA also created a favorable environment for tumor cells by influencing fibroblasts, vascular endothelial cells, and tumor-associated macrophages. Together, increased HA, mainly LMW aids in CLCL progression by affecting tumor cells and microenvironment. Next, bexarotene treatment reduced the amount of total HA in murine tumor-inoculated skin and the supernatant of cultured normal human dermal fibroblasts (NHDFs) and HuT78 cells. Detailed in vitro assessments showed that bexarotene treatment decreased hyaluronic acid synthase (HAS) 1 and HAS2 expression in NHDFs and HAS1, HAS3, and CEMIP in HuT78. Chromatin immunoprecipitation assay revealed bexarotene reduced retinoid X receptor-alpha binding to the HAS1 and HAS2 promoters in NHDFs. Bexarotene potentially exerts its anti-tumor effect by reducing HA through decreased expression of HA synthase. These findings provide us with new insights into the developmental process of CLCT and additional insight into bexarotene treatment.

2024-11-01 | GSE248641 | GEO

Prospective randomized doubleblind assessment of transcriptome modulation by hydrocortisone in severe burn shock

Project description:Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.

2017-07-02 | GSE77791 | GEO

Homo sapiens

Project description:Hydrocortisone and Triiodothyronine Regulate Hyaluronate Synthesis in a Tissue–Engineered Human Dermal Equivalent through Independent Pathways

| PRJNA244086 | ENA

Hydrocortisone induces changes in gene expression and differentiation of immature human enterocytes

Project description:It It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC) including the increased expression of digestive hydrolases. However, the molecular mechanism(s) are not well understood, particularly in human gut. Here we report a microarray analysis of HC- induced changes in gene expression in H4 (a human fetal small intestinal epithelial cell line well-characterized in numerous previous studies). This study identified a large number of HC-affected genes, some involved in metabolism, cell cycle regulation, cell polarity, tight junction formation, and interactions with extracellular matrices. These effects could play an important role in HC-mediated enterocyte maturation in vivo and in vitro. hydrocortisone effect on gene expression prlfile in H4 cells over time (no HC, HC_12h, HC_24h, HC_48h, HC_5d and T84). Six samples are analyzed. Control sample is H4 without HC.

2010-06-16 | E-GEOD-22106 | biostudies-arrayexpress

Effects of Systemically Administered Hydrocortisone on the Human Immunome

Project description:Corticosteroids have been prescribed for decades to modulate inflammation, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or âimmunome,â in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We observed declines in specific B and T cell subsets, and an increase in natural killer cell subsets 4-8 hours after HC. Whole transcriptome profiling revealed a gene expression signature that preceded lymphocyte population changes. We observed decreases in inflammatory cytokines after HC administration. Our study provides insights into the effects of corticosteroids on the human immunome. According to CHI protocols 11-H-0092, 18 healthy volunteers were administered a single dose of intravenous (IV) hydrocortisone at either 50 mg or 250 mg concentrations. PBMC samples were collected immediately prior to receiving the drug (0 hours), then after 1, 4, 8, 12, and 24 hours.

2016-03-14 | E-GEOD-67255 | biostudies-arrayexpress

Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1

Project description:This SuperSeries is composed of the following subset Series: GSE32443: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Affymetrix] GSE32444: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina] Refer to individual Series

2011-10-31 | E-GEOD-32445 | biostudies-arrayexpress

Effects of Systemically Administered Hydrocortisone on the Human Immunome

Project description:Corticosteroids have been prescribed for decades to modulate inflammation, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or “immunome,” in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We observed declines in specific B and T cell subsets, and an increase in natural killer cell subsets 4-8 hours after HC. Whole transcriptome profiling revealed a gene expression signature that preceded lymphocyte population changes. We observed decreases in inflammatory cytokines after HC administration. Our study provides insights into the effects of corticosteroids on the human immunome.

2016-03-14 | GSE67255 | GEO

Hydrocortisone induces changes in gene expression and differentiation of immature human enterocytes

2010-06-03 | GSE22106 | GEO

To study gene expression differences in various dermal equivalents prepared by the individual's laboratory

Project description:We have prepared tissue engineered self assembled dermal equivalents with high similarity to the human dermis (skin). We have manipulated the culture conditions to prepare dermal equivalents with varying amounts of hyaluronic acid and potentially other glycosaminoglycans (GAGs). We are interested in using array technology to determine which genes responsible for carbohydrate and GAG (and if available protein/glycoprotein) synthesis are being either up-or down-regulated in these constructs as compared to a Normal base construct.

2011-10-02 | E-GEOD-32555 | biostudies-arrayexpress

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