To investigate the expression of xenotropic and polytropic retrovirus receptor 1 （） in papillary thyroid cancer （PTC） and its clinical implication. The HPA and UALCAN databases were used to explore the expression of XPR1 in PTC and normal tissues. The cBioPortal database was used to obtain the clinical data of PTC patients and gene expression profile. The correlation of expression with gender，age，sub-types，T stage，N stage，M stage and clinical stage of patients were analyzed. Cox regression was conducted to analysis the factors affecting the prognosis of PTC patients. The mutation of was assessed through cBioPortal database. GO and KEGG analyses were used to explore the related biological pathway of involved in PTC. HPA database analysis showed that XPR1 was highly expressed in PTC tissue compared with normal tissues. UALCAN analysis displayed that expression was significantly higher in PTC tissue compared with normal tissues （<0.01），and the highest and lowest expressions of were observed in tall cell and follicular sub-type of PTC，respectively. The expression of was correlated with age，sub-types，T stage，N stage and disease stage of PTC patients （<0.05 or <0.01），but was not correlated with gender and M stage （all >0.05）. Cox regression analysis showed that was an independent prognostic factor of PTC patients （=2.894，<0.05）. The cBioPortal database indicated that the mutation appeared in 6% PTC patients; the mutation type mainly was missense and the mutation point was located at the E615K. Enrichment analysis indicated that might affect the PTC progression through involvement in metabolic pathway. is highly expressed in PTC tissues，which is associated with the prognosis of patients. Metabolic pathway associated with might play an important role in PTC progression，indicating that might be a novel biomarker for diagnosis and treatment of PTC.
Humans ; Prognosis ; Receptors, G-Protein-Coupled/genetics* ; Receptors, Virus/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure, which may be accompanied by functional or organic damage of heart, brain, kidney and other organs. The pathogenesis and development of hypertension are affected by genetic, environmental, epigenetic, intestinal microbiota and other factors. They are the result of multiple factors that promote the change of blood pressure level and vascular resistance. G protein coupled receptors(GPCRs) are the largest and most diverse superfamily of transmembrane receptors that transmit signals across cell membranes and mediate a large number of cellular responses required by human physiology. A variety of GPCRs are involved in the control of blood pressure and the maintenance of normal function of cardiovascular system. Hypertension contributes to the damages of heart, brain, kidney, intestine and other organs. Many GPCRs are expressed in various organs to regulate blood pressure. Although many GPCRs have been used as therapeutic targets for hypertension, their efficacy has not been fully studied. The purpose of this paper is to elucidate the role of GPCRs in blood pressure regulation and its distribution in target organs. The relationship between GPCRs related to intestinal microorganisms and blood pressure is emphasized. It is proposed that traditional Chinese medicine may be a new way to treat hypertension by regulating the related GPCRs via intestinal microbial metabolites.
Blood Pressure ; GTP-Binding Proteins ; Gastrointestinal Microbiome ; Humans ; Hypertension/genetics* ; Receptors, G-Protein-Coupled/metabolism*

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration

Objective To study the expression and significance of leucine-rich repeat-containing G-protein coupled receptor(LGR)5/6 in childhood acute lymphoblastic leukemia(ALL). Methods A total of 39 children who had ALL and achieved complete remission on day 33 after induction therapy were enrolled.The children before induction therapy were considered as the incipient group,and those who achieved complete remission on day 33 by induction therapy were considered as the remission group.According to the degree of risk,they were assigned into 3 groups:low-risk(
Child ; Humans ; Leucine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; RNA, Messenger/genetics* ; Receptors, G-Protein-Coupled/genetics* ; Wnt Signaling Pathway

Numerous musculoskeletal disorders are caused by thickened ligament, tendon stiffness, or fibrosis of joint capsule. Relaxin, a peptide hormone, can exert collagenolytic effect on ligamentous and fibrotic tissues. We hypothesized that local injection of relaxin could be used to treat entrapment neuropathy and adhesive capsulitis. Because hormonal effect depends on the receptor of the hormone on the target cell, it is important to confirm the presence of such hormonal receptor at the target tissue before the hormone therapy is initiated. The aim of this study was to determine whether there were relaxin receptors in the ligament, tendon, and joint capsular tissues of rats and to identify the distribution of relaxin receptors in these tissues. Transverse carpal ligaments (TCLs), inguinal ligaments, anterior cruciate ligaments (ACLs), Achilles tendons, and shoulder joint capsules were obtained from male Wistar rats. Western blot analysis was used to identify relaxin receptor isoforms RXFP1 and RXFP2. The distribution of relaxin receptors was determined by immunohistochemical staining. The RXFP1 isoform was found in all tissues examined. The RXFP2 isoform was present in all tissues but the TCLs. Its expression in ACLs tissues was relatively weak compared to that in other tissues. Our results revealed that RXFP1 and RXFP2 were distributed in distinctly different patterns according to the type of tissue (vascular endothelial cells, fibroblast-like cells) they were identified.
Animals ; Blotting, Western ; *Gene Expression Regulation ; Immunohistochemistry ; Ligaments/*metabolism ; Male ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled/*genetics/metabolism ; Receptors, Peptide/*genetics/metabolism ; Shoulder Joint/*metabolism ; Tendons/*metabolism

GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells. Their importance to basic cell biology, human diseases, and pharmaceutical interventions is well established. Many crystal structures of GPCR proteins have been reported in both active and inactive conformations. These data indicate that agonist binding alone is not sufficient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins, yet other essential factors remain elusive. Based on analysis of available GPCR crystal structures, we identified a potential conformational switch around the conserved Asp2.50, which consistently shows distinct conformations between inactive and active states. Combining the structural information with the current literature, we propose an energy-coupling mechanism, in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
Binding Sites ; GTP-Binding Proteins ; chemistry ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Membrane Potentials ; Models, Molecular ; Protein Conformation ; Receptors, G-Protein-Coupled ; chemistry ; genetics ; metabolism ; Signal Transduction

OBJECTIVETo study the effects of specific small interfering RNA (siRNA) on Smoothened (Smo) gene expression and the proliferation and apoptosis of colorectal cancer LoVo cells.

METHODSThree different siRNAs (siRNA-1, siRNA-2, and siRNA-3, respectively) were transfected into LoVo cells via cationic liposome, and the changes of Smo mRNA level were determined using semi-quantitative RT-PCR 48 h after transfection. Flow cytometry and MTT assay were performed to assess the effect of the siRNAs on the proliferation and apoptosis of LoVo cells.

RESULTSForty-eight hours after Smo siRNA-1 transfection, Smo mRNA expression in LoVo cells decreased by about 63.56%, a reduction significantly greater than that in cells transfected with the other two siRNAs. The cell proliferation decreased significantly after Smo siRNA-1 transfection in comparison with the control cells, and 48 h after transfection, significantly higher apoptosis rate was observed in Smo siRNA-1-transfected cells than in the control cells.

CONCLUSIONSpecific siRNA can significantly decrease Smo mRNA expression and inhibit the proliferation while inducing apoptosis of LoVo cells.

Apoptosis ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; RNA, Small Interfering ; genetics ; Receptors, G-Protein-Coupled ; deficiency ; genetics ; Smoothened Receptor ; Time Factors ; Transfection

OBJECTIVETo investigate the expression and its significance of melatonin receptor in human hypertrophic scarring.

METHODSThe expression of melatonin receptor GPR50 was detected with immunohistochemistry and the melatonin receptors (MT1, MT2) mRNA were assessed with RT-PCR method in 10 cases of human hypertrophic scar and normal skin. The positive production was sequenced with auto sequencing instrument.

RESULTSPositive signals of melatonin receptor could be found in the cell membrane and cytoplasm. The melatonin receptor GPR50 was located in the epithelial basal cells,sweat gland cells and hair follicle in both hypertrophic scar and normal skin. The melatonin receptor GPR50 was extensively expressed in fibroblasts of hypertrophic scar, but not in fibroblasts in normal skin. RT-PCR showed that the expression of melatonin receptor (MT1, MT2) mRNA in hypertrophic scar was significantly higher than that in normal skin (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was higher than MT2 mRNA (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was 0.99081 +/- 0.26485 and 1.16584 +/- 0.21829 copy number/microl cDNA, respectively; the expression of MT2 mRNA was 0.77083 +/- 0.15927 and 0.99550 +/- 0.14624 copy number/ microl cDNA, respectively. Sequencing results indicated that the positive product coincided with cDNA of human melatonin receptor in GeneBank.

CONCLUSIONSPositive expression of melatonin receptor can be found in human hypertrophic scar and normal skin, but it is higher in scar. The over expression of melatonin receptor in hypertrophic scar may be related to the development of hypertrophic scar.

Adult ; Cicatrix, Hypertrophic ; metabolism ; Female ; Humans ; Male ; Nerve Tissue Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; Receptors, G-Protein-Coupled ; genetics ; metabolism

BACKGROUNDOGR1 was found as a G-protein coupled receptor (GPCR) and proton sensor. Our previous studies have found that OGR1 has inhibitory effect on the metastasis of prostate cancer. In order to investigate the roles of OGR1 gene in the biological activities of ovarian cancer, we studied the OGR1 effects on ovarian cancer cells, HEY cells.

METHODSOGR1 gene was transfected into HEY cell, in which endogenous expression is low. OGR1-overxepressed cells and vector-transfected cells were compared in different assays. Western blotting was employed to confirm the high expression level of OGR1. Cell proliferation was determined by MTT assay and cell doubling time assay. Cell migration assay (transwell assay) and cell adhesion assay were performed to determine the migration and adhesion potential of cells. Student's t test was employed for statistical analysis.

RESULTSProliferation of OGR1-overexpressed cells was significantly reduced (P < 0.01); cell migration was significantly inhibited in the OGR1-transfected cells (P < 0.01); cell adhesion to extracellular matrix including fibronectin, vitronectin, collagen I/IV was significantly increased (P < 0.01).

CONCLUSIONSOGR1 expression in human ovarian cancer cells significantly inhibited the cell proliferation and migration, but significantly enhanced cell adhesion to the extracellular matrix. It indicated that OGR1 may be a tumor suppressor gene for ovarian cancer.

Blotting, Western ; Cell Adhesion ; genetics ; physiology ; Cell Line, Tumor ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; Humans ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Transfection

OBJECTIVETo investigate the expression of urotensin II (U II) and G-protein coupled receptor 14 (GPR14) mRNA in human pheochromocytoma tissues.

METHODSTotal RNA from normal adrenal and pheochromocytoma tissues was extracted. The reverse transcription-polymerase chain reaction method was used to evaluate the levels of U II and GPR14 mRNA expression in human pheochromocytoma tissues.

RESULTSThere was no significant difference of U II and GPR14 mRNA expression between normal adrenal cortex and medulla. The expression of U II and GPR14 mRNA in pheochromocytoma was significantly lower than that in normal adrenal cortex and medulla (P < 0.05). The expression of GPR14 mRNA in adrenal pheochromocytomas was significantly lower than that of extra-adrenal pheochromocytomas (P < 0.05).

CONCLUSIONU II and GPR14 may play a role in the pathogenesis and hypertension regulating of pheochromocytoma.

Adrenal Cortex ; metabolism ; Adrenal Gland Neoplasms ; metabolism ; Adrenal Medulla ; metabolism ; Humans ; Pheochromocytoma ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, G-Protein-Coupled ; biosynthesis ; genetics ; Urotensins ; biosynthesis ; genetics