Abstract:
:Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Gu HP,Lin S,Xu M,Yu HY,Du XJ,Zhang YY,Yuan G,Gao Wdoi
10.1210/en.2012-1114subject
Has Abstractpub_date
2012-08-01 00:00:00pages
3692-700issue
8eissn
0013-7227issn
1945-7170pii
en.2012-1114journal_volume
153pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::A substantial body of experimental evidence indicates that serotonin (5-HT) and several synthetic 5-HT receptor agonists activate the hypothalamic-pituitary-adrenal (HPA) axis. To explore the mechanism(s) by which 5-HT or 5-HT agonists enhance the activity of the HPA axis in vitro, we examined the stimulatory effects ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-4-1888
更新日期:1990-04-01 00:00:00
abstract::We investigated the effect of glucocorticoid on the generation of osteoclasts. In mouse bone marrow culture systems, dexamethasone, a synthetic glucocorticoid analog, enhanced osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in a dose-dependent manner. Conversely, dexamethasone inhibit...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.3.8119150
更新日期:1994-03-01 00:00:00
abstract::Hydrogen peroxide acts as electron acceptor in the oxidative reactions (iodination and coupling) by which the thyroid hormones are formed. Regulation of the generation of H2O2 was studied in monolayer cultures of the FRTL-5 rat thyroid cell line and in primary monolayer cultures of porcine thyroid cells. Both cell typ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.1.1309340
更新日期:1992-01-01 00:00:00
abstract::Primary cultures of enzymatically dispersed rat anterior pituitary cells were used to examine the effect of pure 31 kilodalton bovine inhibin on GnRH-induced up-regulation of GnRH binding sites. After 2 days in culture, the cells were exposed to stimuli with or without test substances for 10 h, followed by evaluation ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-1-363
更新日期:1989-01-01 00:00:00
abstract::To evaluate the possible existence of masked gonadotropin receptors in the corpus luteum, we characterized the effects of alcohols and neuraminidase on [125I]iodohuman LH binding to in vitro preparations of luteal tissue from the rhesus monkey and pseudopregnant rat. The presence of 1-8% (vol/vol) ethanol enhanced spe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-2-747
更新日期:1985-08-01 00:00:00
abstract::Osteoclast precursors have not been well characterized because there are no known markers that can detect them. We have used osteoclast-like cells formed in vitro to develop a panel of specific antibodies that react with mature osteoclasts, osteoclast precursors, and other cells in the osteoclast lineage. Monoclonal a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-2-630
更新日期:1989-08-01 00:00:00
abstract::The control of ACTH secretion by opiates seems to involve stimulatory and inhibitory pathways, since opiate agonists and antagonists are capable of releasing ACTH in conscious rats. To elucidate the role of different opiate receptors in the control of ACTH release, rats were treated with receptor-selective opiate agon...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-6-2688
更新日期:1985-06-01 00:00:00
abstract::Immunoreactive beta-endorphin (ir-beta EP) and immunoreactive N-acetyl-endorphin (ir-NacEP) have been demonstrated in the rat thyroid by specific RIA and characterized by reverse phase HPLC. In addition, pituitary and thyroid ir-beta EP and ir-NacEP levels have been determined after manipulation of the pituitary-thyro...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-2-642
更新日期:1986-08-01 00:00:00
abstract::Thyroid dysfunction during human pregnancy is closely related to serious pregnancy outcome. However, the regulation and function of thyroid hormones during early pregnancy are largely unknown. We found that type II deiodinase, an enzyme converting T4 to activated T3, is highly expressed in the mouse uterus on days 3 a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1015
更新日期:2014-07-01 00:00:00
abstract::The lipid phosphatase, phosphatase and tensin homolog (PTEN), is a key element in controlling cell growth and survival and has a well established role as tumor suppressor protein in many neoplasia. Several data indicate that silencing of PTEN gene expression may be relevant in follicular thyroid cell transformation. T...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-0282
更新日期:2004-10-01 00:00:00
abstract::The paucity of clinical and preclinical studies investigating sex differences in sleep has resulted in mixed findings as to the exact nature of these differences. Although gonadal steroids are known to modulate sleep in females, less is known about males. Moreover, little evidence exists concerning the origin of these...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-1624
更新日期:2014-01-01 00:00:00
abstract::We have previously shown that in reaggregate cell cultures of 14-day-old female rat pituitary, LHRH is capable of stimulating lactotrophs to enter the S-phase of the cell cycle, and that this effect is mediated by paracrine growth factors secreted from gonadotrophs. In the present report we describe the isolation, pur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.1.8013350
更新日期:1994-07-01 00:00:00
abstract::To examine the mechanism of estrogen's direct stimulation of steroidogenesis in the rabbit corpus luteum, we tested the hypothesis that the effect of estrogen on progestin production occurs at the site of processing of the precursor for pregnenolone (i.e. cholesterol) in the mitochondrion. For this purpose, we manipul...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-5-1948
更新日期:1988-05-01 00:00:00
abstract::The effects of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen to various cell types, on proliferation and differentiated functions of the murine Leydig tumor cell line MA-10 were investigated. Kinetic binding experiments at room temperature showed that [125I] ET-1 bound to MA-10 cells and reached equilibriu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.2.8425480
更新日期:1993-02-01 00:00:00
abstract::Specific binding sites for PRL were identified on isolated intestinal epithelial cells from both male and female rabbits. These receptors exhibited a very high affinity for PRL (Kd = 5 x 10(-11) M) and were immunologically very similar to the well characterized mammary PRL receptor. About 3500 PRL receptors/cell were ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.5.1572300
更新日期:1992-05-01 00:00:00
abstract::Prokineticin-1 (PK1) is a recently described protein with a wide range of functions, including tissue-specific angiogenesis, modulation of inflammatory responses, and regulation of hemopoiesis. The aim of this study was to investigate the localization and expression of PK1 and PK receptor-1 (PKR1), their signaling pat...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1695
更新日期:2008-07-01 00:00:00
abstract::PTH secretion is tightly regulated by extracellular calcium ([Ca2+]e) and in turn regulates calcium homeostasis through its action on target tissues. We investigated the mechanism and physiological significance of intracellular calcium ([Ca2+]i) levels in relation to the secretion of PTH in single bovine parathyroid c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.7.7789320
更新日期:1995-07-01 00:00:00
abstract::After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal str...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2131
更新日期:2013-05-01 00:00:00
abstract::Stimulation of rat granulosa cell aromatase activity by FSH has recently been used as a sensitive biological end point to develop an in vitro FSH bioassay. The present report provides a detailed validation and application of this assay. In the presence of androstenedione and diethylstilbestrol, FSH stimulated estrogen...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-4-1570
更新日期:1986-10-01 00:00:00
abstract::Neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus (ARH) have been shown to play an important role in modulating LH secretion. One mechanism by which the ARH NPY system may regulate LH secretion is by modulating GnRH neuronal function. Thus, the present study examined whether the ARH NPY system pr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.11.7093
更新日期:1999-11-01 00:00:00
abstract::Circulating levels of the pancreatic beta-cell peptide hormone amylin and the gut peptide PYY[3-36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown. We report that the combi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0898
更新日期:2007-12-01 00:00:00
abstract::31P nuclear magnetic resonance (NMR) was used to study the effects of 17 beta-estradiol on the content of phosphates and on the flux catalyzed by creatine kinase in immature rat uteri. Perifusion with oxygenated medium at 36 C maintained the uteri in a viable state for at least 10 h in vitro during 31P NMR measurement...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-4-1631
更新日期:1988-04-01 00:00:00
abstract::Exposure of quiescent bovine parathyroid cells to serum or a serum substitute caused an elevation in [3H] thymidine incorporation, followed by an increase in cell number. This was preceded by a rapid transient rise in c-myc and c-fos proto-oncogene mRNA levels. Alterations in the medium calcium concentration had no ef...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-2-935
更新日期:1989-08-01 00:00:00
abstract::GH promotes not only longitudinal growth in children but is active throughout life in protein, fat, and carbohydrate metabolism. The multiple actions of GH start when GH binds to the cell surface-expressed GH receptor. Effectiveness of the hormone depends both on its presence in the circulation and the availability of...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.4.8755
更新日期:2002-04-01 00:00:00
abstract::Hypothyroid animals secrete not only more TSH, but also qualitatively different TSH, with altered oligosaccharides. To explore the cellular mechanism of oligosaccharide modulation by thyroid status, 40 mice were treated without or with propylthiouracil (PTU), and pituitaries were removed after 1, 2, 3, 4, and 6 weeks....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.5.7956920
更新日期:1994-11-01 00:00:00
abstract::Three members of the progestin and adipoQ receptor (PAQR) family, PAQR-7, PAQR-8, and PAQR-5 [membrane progesterone (P4) receptor (PR) (mPR)α, mPRβ, and mPRγ], function as plasma mPRs coupled to G proteins in mammalian cells, but the characteristics of two other members, PAQR6 and PAQR9 (mPRδ and mPRε), remain unclear...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1772
更新日期:2013-01-01 00:00:00
abstract::Atrial, brain-type, and C-type natriuretic peptides (ANP, BNP, and CNP) act via receptors with intrinsic guanylate cyclase activity. The A-type and B-type ANP receptors are selectively activated by ANP and CNP, respectively. The anterior pituitary is a site of ANP production and action, suggesting a local regulatory f...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.5.7682940
更新日期:1993-05-01 00:00:00
abstract::11beta-hydroxysteroid dehydrogenases (11betaHSDs) catalyze interconversion of 11-hydroxy-glucocorticoids with inactive 11-keto metabolites. In blood vessel walls, loss of 11betaHSD1 is thought to reduce local glucocorticoid concentrations, reducing the progression of atheroma and enhancing angiogenesis. Conversely, on...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0996
更新日期:2007-01-01 00:00:00
abstract::Mutations in the GnRH receptor gene (GNRHR) can result in hypogonadotropic hypogonadism in humans. Unlike most mammals, mice lack a second form of GnRH (GnRH2) and a type 2 GnRH receptor. To determine whether the GnRH receptor is critical at all stages of reproduction and whether this receptor has additional physiolog...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0598
更新日期:2010-03-01 00:00:00
abstract::The trace element vanadium (V) exerts insulin-like effects in vitro. The present study examined its effects on glucose homeostasis in rats made diabetic by streptozotocin. Na3VO4 (0.2 or 0.5 mg/ml) was administered ad libitum in drinking water. Fed plasma glucose levels (approximately 26 mmol/liter) fell by 30% and 56...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-4-2048
更新日期:1988-10-01 00:00:00