Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:B6ZGS6 (Retinoid-related orphan receptor gamma)
 5 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoid-related orphan receptor gamma t (RORgamma t) is a member of the nuclear receptor family that is specifically expressed in T cell compartments. RORgamma t regulates the development of T cells in the thymus and the differentiation of effector T cells in the periphery. During T cell development, RORgamma t enhances CD4(+)CD8(+) double positive thymocyte survival by upregulating Bcl-x(L). In the periphery, RORgamma t regulates IL-17 production and dictates the differentiation of pro-inflammatory T helper 17 (T(H)17) cells that play a critical role in inflammatory conditions and autoimmunity. RORgamma t-deficient T cells fail to differentiate into T(H)17 cells, whereas forced expression of RORgamma t is sufficient to induce naive T cells to produce IL-17. T(H)17 cells are believed to be the major inflammatory cells in autoimmune diseases. Therefore, inhibition of RORgamma t activity could potentially alleviate the symptoms associated with the T(H)17-dependent inflammatory autoimmune diseases. RORgamma t is thus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity.
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PMID:Retinoid-related orphan receptor gamma t is a potential therapeutic target for controlling inflammatory autoimmunity. 1750 12

Retinoid-related orphan receptor gamma (RORgamma) is an orphan nuclear hormone receptor (NR) that is preferentially expressed in skeletal muscle and several other tissues, including pancreas, thymus, prostate, liver and testis. Surprisingly, the specific role of RORgamma in skeletal muscle, a peripheral tissue, has not been examined. Muscle is one of the most energy demanding tissues which accounts for ~40% of the total body mass and energy expenditure, >75% of glucose disposal and relies heavily on beta-oxidation of fatty acids. We hypothesize that RORgamma regulates metabolism in this major mass lean tissue. This hypothesis was examined by gain and loss of function studies in an in vitro mouse skeletal muscle cell culture model. We show that RORgamma mRNA and protein are dramatically induced during skeletal muscle cell differentiation. We utilize stable ectopic over-expression of VP16-RORgamma (gain of function), native RORgamma and RORgammaDeltaH12 (loss of function) vectors to modulate RORgamma mRNA expression and function. Ectopic VP16 (herpes simplex virus transcriptional activator)-RORgamma and native RORgamma expression increases RORalpha mRNA expression. Candidate-driven expression profiling of lines that ectopically express the native and variant forms of RORgamma suggested that this orphan NR has a function in regulating the expression of genes that control lipid homeostasis (fatty acid-binding protein 4, CD36 (fatty acid translocase), lipoprotein lipase and uncoupling protein 3), carbohydrate metabolism (GLUT5 (fructose transporter), adiponectin receptor 2 and interleukin 15 (IL-15)) and muscle mass (including myostatin and IL-15). Surprisingly, the investigation revealed a function for RORgamma in the pathway that regulates production of reactive oxygen species.
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PMID:Retinoid-related orphan receptor gamma regulates several genes that control metabolism in skeletal muscle cells: links to modulation of reactive oxygen species production. 1760 83