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MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules.They regulate negatively the expression of target genes at post-transcriptional stages by means of affecting the stability of target mRNA or interfering with the transcriptional process.Recently,there is evidence demonstrating that miRNAs play important roles in the gene expressions of thyrotoxic heart diseases.Elevated levels of thyroid hormones profoundly influence the cardiovascular system through the renin-angiotensin system (RAS).As a principal active component of RAS,angiotensin Ⅱ receptor 1 (AT1 R) interacts with miRNAs in promoting or extenuating the progress of thyrotoxic heart disease.In this article,the roles of AT1R-associated miRNAs,miR-21,miR-155,miR-208a/b,and miR-499 in thyrotoxic heart disease were reviewed.
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Objective To explore the effects of estrogen and angiotensin Ⅱ receptor 1 inhibitor（saralasin）on cell proliferation,cell cycle and apoptosis in endometrial carcinoma cell line HEC-1A.Methods Immunocytochemical assay was applied to detect the expression of AT1-R,PI3K,p-Akt and ERK protein in HEC-1A cell.The effects of estrogen and saralasin on cell proliferation,cell cycle distribution and apoptosis of HEC-1A cell were detected by MTT assay and fluorescence activated cell sorting technique.The expression of ERK and p-Akt protein in HEC-1A cell treated with estrogen and saralasin were analyzed by Western blot.Results The expression of AT1-R,PI3K,pAkt,and ERK protein was found in HEC-1A cell.Estrogen stimulated the proliferation of HEC-1A cell,decreased G0~G1 phase proportion and increased S phase proportion significantly,minimized the number of apoptotic cells,and up-regulated the expression of ERK protein.Saralasin obviously inhibited the proliferation and induced apoptosis of estrogen induced HEC-1A cell,increased G0~G1 phase proportion and decreased S phase proportion,and down-regulated the expression of ERK protein.Conclusion Estrogen could promote the proliferation of HEC-1A cell through AT1-R.AT1-R inhibitor saralasin could inhibit the proliferation and induce the apoptosis of estrogen induced HEC-1A cell.The down-regulation of ERK protein expression by interrupting the mitogen-activated protein kinase（MAPK）signaling pathway might be involved in the possible mechanism.Thus saralasin could be a valid approach to treat ER-negative endometrial carcinoma.
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To evaluate the effect of rosiglitazone on the Angiotensin Ⅱreceptor 1(AT1) and explore its mechanisms of lowering the blood pressure and protecting the organs. The spontaneously hypertensive rats(SHR) 24(SHR)rats were divided into 2 groups:12 were given rosiglitazone,12 were in the control gronp without any treatment. The duration of observation was 8 weeks. The tail blood pressure was measured indirectly.The in situ hybridization and the immunohistochemical methods were used to estimate the expression of the AT1 mRNA and AT1 receptors of heart.In rosiglitazone group,the blood pressure was reduced significantly,and the expressions of AT1 mRNA and AT1 receptor of heart were inhibited.The effect of rosiglitazone on the expressions of AT1 mRNA and AT1 receptor might be one of the reasons why insulin sensilizers reduce the blood pressure and prevent the organ injuries of hypertension.
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Objective To investigate the potential role of angiotensinⅡ(AngⅡ)-angiotensinⅡreceptor 1 (ATRI) pathway on inflammatory activation in the lung of rats. Method Twenty four Sprague-Dawley rats were randomly divided into four groups: control group, Ang II group, AngⅡ+losartan group and losartan group. Lung wet/dry weight (W/D) was recorded to assess lung injury. The total lung homogenates were prepared to detect nuclear factor-kappa B (NF-?B) activation by electrophoretic mobility gel shift assary (EMSA), tumor necrosis factor (TNF)-?mRNA expression by reverse transcription polymerase chain reaction (RT-PCR), myeloperoxidase (MPO) and malondialdehyde (MDA) by colorimetry. Plasma yon Willebrand Factor (vWF) were assessed by enzyme-linked immunosorbent assay (ELISA). Meanwhile, pathological changes were examined under optical microscope. Results Histologically, alveolar edema, hemorrhage, and massive inflammatory cell infiltration were observed in AngⅡgroup, but not in control group and losartan group. Compared with AngⅡgroup, histological injury was lesser in AngⅡ+ losartan group. In AngⅡgroup, lung W/D, NF-?B activation, TNF-?mRNA expression, MPO, MDA and vWF were markedly higher than those in the other three groups. There were not significant differences of lung W/D, NF-?B activation, TNF-?mRNA expression, MPO, MDA and vWF in control group, AngⅡ+ losartan group and losartan group. Conclusions Systemic infusion of AngⅡcould up- regulate inflammatory mediator expression and induce lung injury in rats. AngⅡ, acting mainly through ATRI, induced inflammatory activation in the lung of rats.
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Aim To study the effect of Semen Sojae Preparatum isoflavone(SSPI)on proliferation and JAK2/STAT3 signal transduction pathway in rat vascular smooth muscle cell(VSMC)induced by Angiotensin Ⅱ(AngⅡ).Methods A cell proliferating model of VSMC induced by AngⅡ was established.The proliferation activity of VSMC was analyzed by MTT method.The expressions of angiotensin Ⅱ receptor 1(AT1R) were detected by RT-PCR method.The expressions of JAK2,STAT3 and phosphorylation protein were detected by Western blot.Results 100 ?g?L-1, 200 ?g?L-1 SSPI significantly inhibited the proliferation of VSMC induced by AngⅡ,and down-regulated the mRNA expression of AT1R.200 ?g?L-1 SSPI could significantly down-regulate the protein expressions of p-JAK2,p-STAT3.Conclusions The proliferation of VSMC induced by AngⅡcan be inhibited by SSPI.The mechanisms might be related to down-regulating the expressions of AT1R,and arresting the phosphorylation of JAK2/STAT3 signal transduction pathway.