This SuperSeries is composed of the SubSeries listed below.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesWhite adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sex, Age, Specimen part
View SamplesEnhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, supporting pre-Osx1+ osteoprogenitors as a critical source and target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) is to date an unidentified transcription factor in the osteoblast gene regulatory network that is induced during bone development and bone repair, and acts upstream of Osx in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives critical regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2.
Age, Specimen part
View SamplesHyperthermia is widely used to treat patients with various cancers. The 42.5C is well known as inflection point of hyperthermia and generally up to 42C of hyperthermia is used in clinical case to combine with other therapy. Here, the effects of heat stress at 42 or 44C for 90 min on the gene expression in HSC-3 human oral squamous carcinoma cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44C for 90 min) and followed by incubation for 0, 6, or 12 h at 37C. The percentage of cell death was 5.0 1.5 (mean SD) at 42C for 12 h and 17.4 0.6 at 44C for 12 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44C.
Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells.
Cell line, Treatment, Time
View SamplesWe employed GeneChip analysis to investigate the global gene expression profiles of neutrophils from BM
Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
Specimen part
View SamplesHyperthermia is widely used to treat patients with various cancers. 42.5C is well known as the inflection point of hyperthermia and generally up to 42C of hyperthermia is used in clinical cases combined with other therapies. Here, the effects of heat stress at 42 or 44C for 15 min on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44C for 15 min), followed by incubation for 0, 1, 3 or 6 h at 37C. The percentage of DNA fragmentation was 8.4 2.2 (mean SD) at 42C for 6 h and 21.0 2.0 at 44C for 6 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44C.
Identification of biological functions and gene networks regulated by heat stress in U937 human lymphoma cells.
Specimen part, Cell line, Treatment
View SamplesHyperthermia (41C <) is widely used to treat patients with various cancers. Here, the effects of hyperthermia (42C for 90 min) on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with hyperthermia (42C for 90 min) and followed by incubation for 0, 1, 3 or 6 h at 37C. The percentage of DNA fragmentation was 7.5 0.9 (mean SD), 10.1 0.2, and 17.3 2.3 at the incubation periods of 1, 3, and 6 h, respectively. Of approximately 47,000 probe sets analyzed, the hyperthermia down-regulated 4,214 probe sets and up-regulated 1,334 by a factor 2.0 or greater.
Gene networks involved in apoptosis induced by hyperthermia in human lymphoma U937 cells.
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View SamplesHyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41C for 30 min (mild hyperthermia) on the gene expression in OUMS-36 human normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.
Common gene expression patterns responsive to mild temperature hyperthermia in normal human fibroblastic cells.
Cell line, Treatment
View SamplesHyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41C for 30 min (mild hyperthermia) on the gene expression in Hs68 human skin normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.
Common gene expression patterns responsive to mild temperature hyperthermia in normal human fibroblastic cells.
Sex, Specimen part, Cell line, Treatment
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