ABSTRACT
<p><b>OBJECTIVE</b>MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis.</p><p><b>DATA SOURCES</b>Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms "microRNA", "miR", "transforming growth factor β", "tgf β", "mitogen-activated protein kinase", "mapk", "integrin", "p38", "c-Jun NH2-terminal kinase", "jnk", "extracellular signal-regulated kinase", "erk", and "fibrosis".</p><p><b>STUDY SELECTION</b>Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis.</p><p><b>RESULTS</b>Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis, such as immune cell sensitization, effector cell activation, and extracellular matrix remodeling. Moreover, several important molecular signaling pathways involve in fibrosis, such as the transforming growth factor-beta (TGF-β) pathway, mitogen-activated protein kinase (MAPK) pathways, and the integrin pathway are regulated by miRNAs. Third, regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart, lung, liver, and kidney. Interestingly, the actions of many drugs on the human body are also induced by miRNAs. It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways, thereby protecting the structures and functions of different organs.</p><p><b>CONCLUSIONS</b>miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases.</p>
Subject(s)
Animals , Humans , Extracellular Signal-Regulated MAP Kinases , Genetics , Metabolism , Fibrosis , Genetics , Metabolism , MicroRNAs , Genetics , Mitogen-Activated Protein Kinases , Genetics , Metabolism , Transforming Growth Factor beta , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the regulatory effects of Shenfu Injection (SFI, ) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure (CHF).</p><p><b>METHODS</b>Forty-five healthy Wistar rats were randomized into three groups: sham, heart failure (model) and SFI group. The CHF was induced by left coronary artery ligation. Seven days after the surgical operation, animals in the sham group and the model group received saline (6.2 mL/kg/d), while animals in the SFI group received SFI (6.2 mL/kg d) intraperitoneally. Four weeks later, cardiac hemodynamic parameters were measured via the carotid route. The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS).</p><p><b>RESULTS</b>Recording of hemodynamic parameters showed that left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure (+dp/dtmax) rise, and maximum rate of left ventricular pressure (-dp/dtmax) decrease, while the left ventricular end diastolic pressure (LVEDP) rose in the model group compared to those in the sham group (P <0.05). The results of the MALDI-TOF MS indicated that haptoglobin (HP), pentraxin 3 (PTX3) and alpha-1-antitrypsin were up-regulated, while serum albumin and 40S ribosomal protein were down-regulated in the model group (P <0.05). Compared with the model group, LVSP, +dp/dtmax and -dp/dtmax were higher, while LVEDP was lower in the SFI group (P<0.05). Expression levels of HP and PTX3 were lower than in the model group (P<0.05).</p><p><b>CONCLUSION</b>SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF. The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure, and they could also be the serum protein targets of SFI.</p>
Subject(s)
Animals , Male , Blood Proteins , Metabolism , C-Reactive Protein , Metabolism , Chronic Disease , Drugs, Chinese Herbal , Therapeutic Uses , Electrophoresis, Gel, Two-Dimensional , Haptoglobins , Metabolism , Heart Failure , Blood , Drug Therapy , Heart Function Tests , Hemodynamics , Hydrogen-Ion Concentration , Imaging, Three-Dimensional , Inflammation , Drug Therapy , Myocardial Ischemia , Blood , Drug Therapy , Phytotherapy , Proteome , Metabolism , Rats, Wistar , Serum Amyloid P-Component , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development.