Biomedical subjects

Wei Jiang

Publications and source records attributed to Wei Jiang.

At least 91 records · Page 5Linked to original sources

PubMed2005

Mild hypothermia protects against sodium taurocholate (NaTc)-induced acute pancreatitis in rats with adverse effects on serum cytokines.

OBJECTIVES: To test the effect of mild hypothermia in reducing pancreatic damage and improving the survival of acute hemorrhagic and necrotic pancreatitis (AHNP) in rats. METHODS: Thirty-six male Sprague-Dawley rats were studied. Sham animals (n = 12) received laparotomy and normothermia; for AHNP with normothermia (n = 12), the core temperature was maintained at 37 degrees C to 37.5 degrees C after AHNP for 2 to 5 hours; for AHNP with hypothermia (n = 12), the core temperature was maintained at 32 degrees C to 33 degrees C afterward. Serum amylase and lipase, interleukin (IL)-1beta, and tumor necrosis factor (TNF-alpha) were measured. The pancreas was examined histologically. In a separate experiment, the core temperature was kept either in normothermia (n = 20) or mild hypothermia (n = 20) for 12 hours after the induction of AHNP; the animals were then returned to their cage. The survival rate was monitored up to 72 hours. RESULTS: Mild hypothermia significantly decreased the release of serum amylase and lipase compared with AHNP normothermia at 2 and 5 hours. Histology examination revealed significantly less tissue damage in AHNP hypothermia. There was a further increase in TNF-alpha and IL-1beta in AHNP in animals with hypothermia compared with normothermia animals. The application of mild hypothermia significantly improved the survival in animals induced with AHNP. CONCLUSIONS: Mild hypothermia decreases amylase and lipase release and improves a survival of AHNP in rats.

Acute Disease↗

PubMed2005

Impaired monocyte maturation in response to CpG oligodeoxynucleotide is related to viral RNA levels in human immunodeficiency virus disease and is at least partially mediated by deficiencies in alpha/beta interferon responsiveness and production.

The biological activity of CpG oligodeoxynucleotide 2216 (ODN2216), a Toll-like receptor 9 agonist, was investigated with monocytes from human immunodeficiency virus (HIV)-negative and HIV-positive (HIV+) donors. Exposure of peripheral blood mononuclear cells to CpG ODN2216 led to decreased expression of the monocyte marker CD14 and increased expression of the dendritic cell marker CD83, as well as increased expression of HLA-DR, CD40, CD80, and CD86 among the monocytes. Several features of the CpG ODN-induced maturation were diminished in monocytes from HIV+ donors, and these deficiencies were related to increased viremia but not to CD4 cell counts. Alpha interferon (IFN-alpha) was implicated as at least a partial mediator of the CpG ODN-induced monocyte maturation. Reduced production of IFN-alpha in response to CpG ODN and reduced frequencies of plasmacytoid dendritic cells, the principal IFN-alpha-producing cell type in peripheral blood, were observed in peripheral blood mononuclear cells from HIV+ donors. These deficiencies also were related to levels of plasma HIV RNA. Responses of monocytes from HIV+ donors to direct stimulation with IFN-alpha also were partially impaired. Thus, reduced production of IFN-alpha and reduced IFN-alpha responsiveness may contribute to diminished functional responses to CpG ODN in HIV disease. Application of CpG ODNs in HIV disease for adjuvant or immunoregulatory purposes may be particularly useful for HIV+ donors without high-level viremia.

Adjuvants, Immunologic↗

PubMed2005

IRIP, a new ischemia/reperfusion-inducible protein that participates in the regulation of transporter activity.

We report the identification and characterization of a new ischemia/reperfusion-inducible protein (IRIP), which belongs to the SUA5/YrdC/YciO protein family. IRIP cDNA was isolated in a differential display analysis of an ischemia/reperfusion-treated kidney RNA sample. Mouse IRIP mRNA was expressed in all tissues tested, the highest level being in the testis, secretory, and endocrine organs. Besides ischemia/reperfusion, endotoxemia also activated the expression of IRIP in the liver, lung, and spleen. The transporter regulator RS1 was identified as an IRIP-interacting protein in yeast two-hybrid screening. The interaction between IRIP and RS1 was further confirmed in coimmunoprecipitation assays. A possible role of IRIP in regulating transporter activity was subsequently investigated. IRIP overexpression inhibited endogenous 1-methyl-4-phenylpyridinium (MPP+) uptake activity in HeLa cells. The activities of exogenous organic cation transporters (OCT2 and OCT3), organic anion transporter (OAT1), and monoamine transporters were also inhibited by IRIP. Conversely, inhibition of IRIP expression by small interfering RNA or antisense RNA increased MPP+ uptake. We measured transport kinetics of OCT2-mediated uptake and demonstrated that IRIP overexpression significantly decreased V(max) but did not affect K(m). On the basis of these results, we propose that IRIP regulates the activity of a variety of transporters under normal and pathological conditions.

Amino Acid Sequence↗

PubMed2005

Cloning and functional analysis of the sequences flanking mini-Tn5 in the magnetosomes deleted mutant NM4 of Magnetospirillum gryphiswaldense MSR-1.

A magnetosome deleted mutant NM4 of Magnetospirillum gryphiswaldense MSR-1 was generated by mini-Tn5 transposon mutagenesis, and a 5045-bp fragment flanking mini-Tn5 in NM4 was cloned by Anchored PCR. Sequencing analysis showed that this fragment involved six putative open reading frames (ORFs); the mini-Tn5 was inserted into ORF4. Functional complementary test indicated that the 5045-bp fragment was required for biosynthesis of magnetosomes in M. gryphiswaldense MSR-1. The protein encoded by ORF4 had 25% of identity with the chemotaxis protein CheYIII of Caulobacter crescentus CB15, and the protein encoded by ORF4 contained a conserved signal receiver domain that can receive the signal from the sensor partner of the bacterial two-component systems. It was suggested that the protein encoded by ORF4 may take part in the signal transduction relating to biosynthesis of magnetosomes.

Amino Acid Sequence↗

PubMed2005

Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid.

Experimental induction of embryonic stem cells (ESCs) to become pancreatic beta cells can potentially provide ample resource for cell transplantation therapy of type I diabetes mellitus. Most of the previously reported induction strategies were long and complicated, and some required genetic manipulation. Moreover, it has been indicated that the insulin staining of ESC progeny was insulin uptake from the culture medium. Here we show that a simple three-step experimental approach based on the combination induction by activin A, all-trans retinoic acid, and other mature factors is able to induce murine ESCs to differentiate into insulin-producing cells in 2 weeks, and that insulin release of these induced cells is regulated by the glucose concentration. Our insulin-enhanced green fluorescent green protein reporter system excludes the possibility of insulin uptake. Transplantation of these ESC-derived insulin-positive cells can normalize blood glucose levels and rescue the survival of streptozocin-induced diabetic mice. The findings reported here offer a novel in vitro model to study the differentiation mechanism of pancreatic beta cells and a potential source of insulin-producing cells for transplantation therapy of type I diabetes mellitus.

Activins↗

PubMed2005

Gene therapy for bone regeneration.

Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone has the unique ability to regenerate and continuously remodel itself throughout life. However, clinical situations arise when bone is unable to heal itself, as with segmental bone loss, fracture non-union, and failed spinal fusion. This leads to significant morbidity and mortality. Current attempts at improved bone healing have been met with limited success, fueling the development of improved techniques. Gene therapy in many ways represents an ideal approach for augmenting bone regeneration. Gene therapy allows specific gene products to be delivered to a precise anatomic location. In addition, the level of transgene expression as well as the duration of expression can be regulated with current techniques. For bone regeneration, the gene of interest should be delivered to the fracture site, expressed at appropriate levels, and then deactivated once the fracture has healed. Delivery of biological factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results both in animal and clinical studies. There has also been tremendous work on discovering new growth factors and exploring previously defined ones. Finally, significant advances are being made in the delivery systems of the genes, ranging from viral and non-viral vectors to tissue engineering scaffolds. Despite some public hesitation to gene therapy, its use has great potential to expand our ability to treat a variety of human bone and musculoskeletal disorders. It is conceivable that in the near future gene therapy can be utilized to induce bone formation in virtually any region of the body in a minimally invasive manner. As bone biology and gene therapy research progresses, the goal of successful human gene transfer for augmentation of bone regeneration draws nearer.

Animals↗

PubMed2005

[Effects of glycosides of Tripterygium wilfordii, methyltestosterone and zhuanggushenjin capsule on nitric oxide synthase in rat testes].

OBJECTIVE: To investigate the effects of glycosides of tripterygium wilfordii (GTW), methyltestosterone and Zhuanggushenjin capsule on nitric oxide synthase (NOS) in rat testes. METHODS: Forty-five rats were equally divided into 5 groups, and respectively given GTW [10 mg/(kg x d)], methyltestosterone [2 mg/(kg x d)], Zhuanggushenjin capsule [0.3 g/(kg x d)], distilled water plus Tween 80 (control I), and distilled water alone (control II) for 4 weeks. At the end of the 5th week, the immunochemical ABC method was used to observe the effects of the three drugs on the NOS positive Leydig cells of the rats. RESULTS: Compared with control II, the GTW group had a significant decrease in the numbers of nNOS and eNOS positive Leydig cells, the methyltestosterone group showed an increase in the number of nNOS but a decrease in that of eNOS positive Leydig cells, and the Zhuanggushenjin group had an increase in the numbers of both nNOS and eNOS positive Leydig cells. CONCLUSION: GTW can reduce NO production by inhibiting eNOS and nNOS, and hence influence the spermatogenic process. Zhuanggushenjin capsule plays an important role in improving male sexual function by enhancing nNOS and eNOS expression and NO synthesis.

Animals↗

PubMed2005

[Effects of moderate hypothermia on expression of nuclear factor-KappaB in rats with acute pancreatitis].

OBJECTIVE: To observe the dynamic changes in the DNA binding activity of nuclear factor-KappaB (NF-KappaB) in rat pancreatic and lung tissues in acute hemorrhagic necrotizing pancreatitis (AHNP), and investigate the effects of moderate hypothermia on AHNP-induced NF-KappaB binding activity in a time-dependent fashion. METHODS: A group of 24 rats was randomly divided into control group, 2, 5 or 12 hours groups after reproduction of AHNP. NF-KappaB binding activity in pancreas and lung tissues was determined using electrophoretic mobility shift assay (EMSA). In another group of 36 rats were randomized into three groups with equal number: sham-operated rats which were kept under 37-37.5 degrees C after laparotomy; AHNP rats with normothermia (37-37.5 degrees C); AHNP rats with moderate hypothermia (32-33 degrees C). Activity of NF-KappaB was assessed at 2 or 5 hours after reproduction of pancreatitis. RESULTS: DNA binding activity of NF-KappaB in pancreas and lung tissue of AHNP rats gradually increased after the development of pancreatitis, and NF-KappaB binding activity was more prominent in pancreas than that in lung tissue at each time point (all P<0.01). NF-KappaB binding activity was inhibited at 2 and 5 hours of moderate hypothermia in lung tissue (P<0.01), but there was no difference in pancreatic tissue between normothermic and hypothermic rats at each time point. CONCLUSION: These data suggest that the expression of NF-KappaB is significantly increased after the development of AHNP. Moderate hypothermia could inhibit the expression of NF-KappaB in lung tissue in acute pancreatitis.

Animals↗

PubMed2005

[Progress of study on inhibitory effects of traditional Chinese herbs on growth factor induced proliferation of vascular smooth muscle cells].

This paper sums up some studies in the last decade regarding the inhibitory effects of traditional Chinese herbs on growth factor induced proliferation of vascular smooth muscle cell (VSMC) via directly measuring the mRNA expression of its growth factors and the related receptors by electron microscope, immunohistochemistry, blot and hybridization in situ.

Cell Proliferation↗

PubMed2005

[Plasma level and prognostic significance of VEGF, bFGF and MMP-9 in patients with advanced non-small-cell lung cancer].

OBJECTIVE: To measure plasma levels of VEGF, bFGF and MMP-9 in advanced non-small-cell lung cancer (NSCLC) patients and evaluate their prognostic value. METHODS: The plasma levels of VEGF, bFGF and MMP-9 in 46 cases with advanced NSCLC were measured by ELISA before chemotherapy and in 30 cases after chemotherapy. RESULTS: The plasma levels of VEGF, bFGF and MMP-9 in patients before chemotherapy were significantly higher than those in healthy control persons (P < 0.05). The correlation between plasma levels of VEGF and bFGF was significant, Spearman's r = 0.329 (P = 0.027). No correlation was found among the levels of angiogenic factors studied above and the following clinical parameters such as age, sex, histological subtype, differentiation of tumor cells, TNM-stage and also blood leukocyte, hemoglobin and platelet counts. The plasma level of MMP-9 in patients with extensive metastasis (including bone metastasis) was significantly higher than that in patients with bone metastasis only (P = 0.013). Reduction of plasma bFGF level after chemotherapy was a unique independent good prognostic factor (RR = 11.737, P = 0.02). CONCLUSION: The measurement of plasma levels of such angiogenic factors as VEGF, bFGF and MMP-9 in advanced NSCLC is helpful for prediction of metastasis tendency and evaluation of prognosis.

Adult↗

PubMed2005

[Effects of land use structure change on regional ecological health--taking Shapingba County as an example].

Land resource is the carrier for the exchange of matter, energy and information flows, while the change velocity and the intensity of land use has strong effects on the ecological processes such as matter circulation, energy flow, and biologic diversity. Land use structure change will alter the type, area, and spatial distribution of ecosystem, and in the meantime, result in the changes of regional ecological health. Employing the principles and methods of landscape ecology, and through endowing relative ecological value to land use type, this paper analyzed the charaeteristics of recent 10 years land use change in Shapingba County of Chongqing, and discussed the effects of land use change on regional ecological health, aimed to provide scientific references for land use planning and sustainable land resource utilization. The results indicated that transformation often occurred among different land use types, and the land use structure in each transformation phase differed quite obviously. Under different land use structure, there was a great disparity in relative ecological value of sub-ecosystems, which played various roles in regional ecological health. In general, the regional relative ecological value embodied both increase and decrease. In the future, the relative ecological value of sub-ecosystem would represent three tendencies, i.e., increase first and decrease then, continuous decrease, and continuous increase. The situation of regional ecological health would gradually become better.

Biodiversity↗

PubMed2005

[Detection of the 30 base pair deletion of Epstein-Barr virus latent membrane protein 1 in extranodal nasal type NK/T-cell lymphoma and its prognostic significance].

OBJECTIVE: To compare the detection rate of Epstein-Barr virus latent membrane protein 1 (LMP1) 30 base pair deletion in extranodal nasal type NK/T-cell lymphoma with that in chronic inflammation of nasopharynx and tonsillitis; and to analyze the prognostic significance of LMP1 deletion in extranodal nasal type NK/T-cell lymphoma. METHODS: Polymerase chain reaction was used to detect the deletion of LMP1 in 55 cases of extranodal nasal type NK/T-cell lymphoma and 19 cases of chronic inflammation of nasopharynx and tonsillitis. Follow-up information of 1 to 58-month duration was available in 33 patients. RESULTS: In all the 55 extranodal nasal type NK/T-cell lymphoma cases studied, 9 cases contained the wide-type or predominantly wide-type LMP1. On the other hand, 46 cases contained the deleted or predominantly deleted LMP1. In the non-lymphoma control group, 16 cases contained the deleted or predominantly deleted LMP1. However, no statistically significant difference was found in the detection rate of 30 base pair deleted LMP1 between extranodal nasal type NK/T-cell lymphoma and control group (P > 0.05). The prognosis of deleted or predominantly deleted LMP1 in extranodal nasal type NK/T-cell lymphoma was worse. CONCLUSION: Though 30 base pair deletion of Epstein-Barr virus LMP1 may not be an important pathogenetic step in extranodal nasal type NK/T-cell lymphoma, it may play some role in tumor progression.

Adolescent↗

PubMed2005

[Expression of bcl-10 protein in MALT lymphoma].

OBJECTIVE: To investigate the significance of bcl-10 protein expression in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Sixty-two cases of MALT lymphoma were reviewed and immunohistochemical studies for bcl-10 and Ki-67 were performed. RESULTS: Sixty out of the 62 cases studied (96.8%) were positive for bcl-10. Thirty-three (53.2%) showed bcl-10 expression in both the nuclei and cytoplasm, while 27 cases (43.6%) showed only cytoplasmic staining. The 10 cases with Hashimoto's thyroiditis demonstrated bcl-10 expression in the cytoplasm. The mean age of patients with bcl-10 nuclear expression (51.4 years old) was 5.2 years younger than those (56.6 years) without bcl-10 nuclear expression. The former category also showed a male predilection (male to female ratio = 19:14, in contrast to 10:19 in the latter category). The frequency of bcl-10 nuclear expression was lower in cases from thyroid but higher in cases from lung, stomach and intestine (P < 0.05). There was no statistically significant correlation between bcl-10 nuclear expression and clinical tumor stage (P > 0.05) or tumor cell morphology (P > 0.05). Amongst the 40 cases of gastrointestinal MALT lymphoma, bcl-10 nuclear expression correlated with extent of tumor involvement. The protein was expressed in 36.4% (4 out of 11 cases) of MALT lymphoma confined to mucosa or submucosa, 65.2% (15 out of 23 cases) of those invading down to muscularis propria or subserosa, and 100% (all 6 cases) of those extending beyond serosa (P < 0.05). There was no statistically significant difference in Ki-67 proliferative index between bcl-10-positive and bcl-10-negative groups (P < 0.05). Follow-up data were available in 52 patients (83.9%) and the five-year survival rate was no statistically significant difference in survival between bcl-10-positive (29 patients, 96.3%) and bcl-10-negative groups (23 patients, 66.4%, P > 0.05). CONCLUSIONS: Two expression patterns of bcl-10 protein were observed in MALT lymphoma: mixed nuclear-cytoplasmic and cytoplasmic only. The bcl-10 nuclear expression appears more important and correlates with anatomic site of tumor and extent of tumor involvement. Immunohistochemical detection of bcl-10 may carry some diagnostic and prognostic implications in assessment of MALT lymphoma.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis.

The spindle midzone, a conspicuous network of antiparallel interdigitating nonkinetochore microtubules between separating chromosomes, plays a crucial role in regulating the initiation and completion of cytokinesis. In this study, we report the use of time-lapse microscopy and a human kinesin endoribonucleases RNase III-prepared short interfering RNA (esiRNA) library to identify Kif4 as a motor protein that translocates PRC1, a spindle midzone-associated cyclin-dependent kinase substrate protein, to the plus ends of interdigitating spindle microtubules during the metaphase-to-anaphase transition. We show that Kif4 binds to PRC1 through its "stalk plus tail" domains and Kif4 and PRC1 colocalize on the spindle midzone/midbody during anaphase and cytokinesis. Suppression of Kif4 expression by Kif4 esiRNA results in the inhibition of PRC1 translocation, a block of the midzone formation, and a failure of cytokinesis. PRC1 translocation and midzone formation can be restored, and the cytokinetic defects can be rescued in Kif4 esiRNA-treated cells by coexpression of Kif4 but not its motor dead mutant Kif4md. Furthermore, we show that cyclin-dependent kinase phosphorylation of PRC1 controls the timing of PRC1 translocation by Kif4. These results, in light of the crucial role of PRC1 in midzone formation, indicate that cell cycle-dependent translocation of PRC1 by Kif4 is essential for midzone formation and cytokinesis.

Cell Cycle↗

PubMed2004

Elucidation of functional groups on gram-positive and gram-negative bacterial surfaces using infrared spectroscopy.

Surface functional group chemistry of intact Gram-positive and Gram-negative bacterial cells and their isolated cell walls was examined as a function of pH, growth phase, and growth media (for intact cells only) using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Infrared spectra of aqueous model organic molecules, representatives of the common functional groups found in bacterial cell walls (i.e., hydroxyl, carboxyl, phosphoryl, and amide groups), were also examined in order to assist the interpretation of the infrared spectra of bacterial samples. The surface sensitivity of the ATR-FTIR spectroscopic technique was evaluated using diatom cells, which possess a several-nanometers-thick layer of glycoprotein on their silica shells. The ATR-FTIR spectra of bacterial surfaces exhibit carboxyl, amide, phosphate, and carbohydrate related features, and these are identical for both Gram-positive and Gram-negative cells. These results provide direct evidence to the previously held conviction that the negative charge of bacterial surfaces is derived from the deprotonation of both carboxylates and phosphates. Variation in solution pH has only a minor effect on the secondary structure of the cell wall proteins. The cell surface functional group chemistry is altered neither by the growth phase nor by the growth medium of bacteria. This study reveals the universality of the functional group chemistry of bacterial cell surfaces.

Bacillus↗

PubMed2004

Changes in production and metabolism of brain natriuretic peptide in rats with myocardial necrosis.

In this study, we employed rat model of acute myocardial necrosis induced by isoproterenol (ISO) to study the possible roles of corin, the protease uniquely distributing in myocardium to convert pro-brain natriuretic peptide (proBNP) to BNP, and neutral endopeptidase (NEP), the major enzyme to degrade BNP, in changing the levels of BNP. In rats with isoproterenol alone, the myocardium necrosis occurred and the cardiac function was inhibited; the BNP contents in plasma and myocardium were upregulated, so did the myocardial corin mRNA level; the NEP activity in plasma and myocardium were downregulated. Omapatrilat (OMA) treatment relieved myocardial lesions and improved cardiac function. In the plasma and myocardium, omapatrilat treatment increased BNP contents, reduced NEP activity; in myocardium, mRNA level of proBNP and corin decreased, but NEP mRNA expression increased. Our study confirmed that omapatrilat treated myocardial necrosis effectively and suggested that increased BNP in rats with myocardial necrosis could depend on increased production and conversion as well as decreased degradation.

Animals↗

PubMed2004

Prognostic value of anxiety and depression in patients with chronic heart failure.

BACKGROUND: Anxiety is often present with depression and may be one of its manifestations. Although the adverse effects of depression in patients with chronic heart failure (CHF) have been well studied, the relation between anxiety and CHF prognosis has not been addressed. In a secondary analysis of data collected for a published study of depression and prognosis in patients with CHF, we examined the relations among anxiety, depression, and prognosis. METHODS AND RESULTS: We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of cardiac events. We followed up these patients for all-cause mortality over 1 year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A) were identical at 33.5; the mean BDI score was 8.7+/-7.6. State-A and Trait-A scores correlated highly with each other (r=0.85; P<0.01) and with BDI score (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with and without confounding variables showed no relation between State-A or Trait-A and 1-year mortality. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase; P<0.01). CONCLUSIONS: Although anxiety and depression are highly correlated in CHF patients, depression alone predicts a significantly worse prognosis for these patients.

Aged↗

PubMed2004

Effects of adrenomedullin on aldosterone-induced cell proliferation in rat cardiac fibroblasts.

Aldosterone induces cardiac remodeling in cardiovascular diseases by stimulating the proliferation, production and secretion of collagen in fibroblasts. It also stimulates vascular smooth muscle cells to produce and secrete adrenomedullin (ADM), which has a cytoprotective effect against cardiovascular damage. We examined the effect of aldosterone on ADM production and secretion in rat cardiac fibroblasts, and the effect of ADM on aldosterone-stimulated fibroblast proliferation to observe the interaction between endogenous ADM and aldosterone. We detected ADM produced and secreted from cultured cardiac fibroblasts and the intracellular cAMP level by radioimmunoassay; evaluated cell proliferation by the level of [3H]-thymine incorporation; measured preproADM gene expression by reverse transcriptase polymerase chain reaction (RT-PCR); and monitored extracellular signal related kinase (ERK) activity by the phosphorylation of myelin basic protein in the presence of [gamma-32P] ATP. Our results showed that aldosterone-stimulated secretion of ADM and its mRNA expression were concentration-dependent, which could be inhibited by the specific antagonist of mineralocorticoid receptor, spironolactone. In contrast, ADM inhibited aldosterone-induced fibroblast proliferation and ERK activity. Treatment with ADM24-50 (a new antagonist of specific ADM receptors) and calcitonin gene-related peptide (CGRP)8-37 (the antagonist of CGRP receptor type 1), to attenuate the action of endogenous ADM, reinforced the aldosterone-induced proliferation and inhibited the intracellular cAMP production stimulated by aldosterone. Thiorphan, an inhibitor of ADM degradation, inhibited the [3H]-thymine incorporation and reinforced the intracellular cAMP level induced by aldosterone. We reach the conclusion that aldosterone stimulates rat cardiac fibroblasts to produce and secrete ADM, which in turn regulates the proliferation-induced effects of aldosterone in these cells.

Adrenomedullin↗