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    Investigating The Role of hsa-miR-147 as Therapeutic target in JAK/STAT pathway In Hypertension

  • Setare Samizade,1,* Alireza Nasr Esfahani,2
    1. Department of Molecular and Cell Biochemistry, Falavarjan Branch , Islamic Azad University, Isfahan , Iran
    2. Department of Molecular and Cell Biochemistry, Falavarjan Branch , Islamic Azad University, Isfahan , Iran


  • Introduction: Hypertension is a major public health problem among the elderly population worldwide that is related to increasing risk of adverse cardiovascular events which is a major risk factor for the development of stroke, coronary artery disease, heart failure, and chronic renal failure. Diagnosis and treatment progression have key role in exploration of biomarkers for hypertension. MicroRNAs are small non-coding RNAs that regulate post-transcriptional gene expressions. They have been shown to play an important role in fibrogenic process in multiple organs.so this study aims to investigate the relationship between hypertension and microRNAs in JAK/STAT pathway.
  • Methods: By using mirbase, HMDD and miRdSNP, miRNA properties were obtained. The miRTarBase, MIRWALK2.0 and TargetScan, target genes were identified. Venn diagram used to identify common target genes between MiRNAs. Using DAVID and KEGG, signal paths were obtained and the pathways associated with diabetes were interpreted. The gene network was obtained through GENE MANIA.
  • Results: We identified hsa-miR-23a-5p as the best miRNA, its target genome and associated cell signaling pathways. Then, the findings presented that binding of the cytokine (IL-6 or IL-11) to its unique receptor (IL-6R or IL-11R) triggers the homo dimerization of GP130. This results that hsa-miR-147 phosphorylates JAK1, JAK2, and Tyk2, which phosphorylate intracellular tyrosine residues that serve as docking sites for STAT3 in hypertension .ET1 and Ang II exert their action through the activation of receptors that belong to a large family of transmembrane guanine nucleotide-binding protein-coupled receptors (GPCRs). JAK and STAT are constitutively expressed by hsa-miR-147 and directly coupled to this receptor. The binding of ETI/Ang II which is activated by hsa-miR-147, induces the phosphorylation of tyrosine in the JAK2 kinases, which in turn activates STAT1 and STAT3. In addition, hsa-miR-147 can stimulate the activity of PKC δ by activating ET-1, which phosphorylates STAT3.
  • Conclusion: : Hypertension is a disease that affects the pulmonary vasculature, increasing pulmonary vascular resistance and pulmonary pressure, which leads to compensatory right ventricular hypertrophy that can turn into right ventricular failure. The JAK/STAT pathway is crucial in transmitting signals from many cytokines and growth factors into the nucleus regulating gene expression and functions. In this study we found that the role of hsa-miR-147 in hypertension is associated with the JAK/STAT pathway in which hsa-miR-147 might be a novel bio-marker for hypertension. The potential role of miR-21 as a new target for predicting and treating hypertension is also explored.
  • Keywords: Hypertension, JAK/STAT pathway, MicroRNA, Target genes