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      The effects of kisspeptin-10 on serum metabolism and myocardium in rats

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          Abstract

          Kisspeptin is a peptide encoded by the Kiss 1 gene and is also called metastin. Previous studies have generally focused on several functions of this peptide, including metastasis, puberty, vasoconstriction and reproduction. However, few studies have focused on the cardiac functions of kisspeptin. In the present study, cardiac histomorphology was observed via TEM (transmission electron microscope) and HE and Masson staining to observe instinctive changes. Serum metabolites levels were also measured and analyzed using GC/TOF-MS after injection with kisspeptin-10. A gene chip was employed to screen the potential genes and pathways in the myocardium at the transcriptional leve, while RT-PCR and Western Blot were conducted to verify the relevant mRNA and protein expression, respectively. Histopathological findings demonstrated that there were many irregular wavy contractions through HE staining and increased fibrosis around the heart cells through Masson staining after treatment with kisspeptin-10. Additionally, the main changes in ultrastructure, including changes in mitochondrial and broken mitochondrial cristae, could be observed with TEM after treatment with kisspeptin-10. The PCA scores plot of the serum metabolites was in the apparent partition after injection of kisspeptin-10. Twenty-six obviously changed metabolites were detected and classified as amino acids, carbohydrate metabolites, organic acids and other metabolites. Furthermore, gene chip analysis showed 1112 differentially expressed genes after treatment with kisspeptin-10, including 330 up-regulated genes and 782 down-regulated genes. These genes were enriched in several signaling pathways related to heart diseases. The RT-PCR result for ITGB8, ITGA4, ITGB7, MYL7, HIF1-α and BNP corresponded with the gene chip assay. Moreover, the upregulated genes ITGB8, ITGA4 and BNP also displayed consistent protein levels in Western Blot results. In summary, these findings suggest that kisspeptin-10 could alter the morphology and structure of myocardial cells, serum metabolite levels, and expression of genes and proteins in heart tissues. Our work determined the profound effects of kisspeptin-10 on the heart, which could further lead to the development of therapeutics related to kisspeptin-10, including antagonists and analogs.

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          Most cited references 61

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              Focal adhesion kinase: in command and control of cell motility.

              A central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility. Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility. Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 July 2017
                2017
                : 12
                : 7
                Affiliations
                [1 ] College of Veterinary Medicine, Nanjing Agriculture University, Nanjing, China
                [2 ] Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
                Max Delbruck Centrum fur Molekulare Medizin Berlin Buch, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JS YZ.

                • Data curation: YZ XW JP ZL.

                • Formal analysis: JS ZL.

                • Funding acquisition: JS.

                • Investigation: YZ YH ZM CS XL ZZ CJ.

                • Methodology: JS YH.

                • Project administration: JS.

                • Resources: JS ZL.

                • Supervision: JS.

                • Validation: JS.

                • Writing – original draft: YZ.

                PONE-D-17-06867
                10.1371/journal.pone.0179164
                5503227
                28692647
                © 2017 Zhang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Counts
                Figures: 8, Tables: 2, Pages: 19
                Product
                Funding
                Funded by: The Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
                Award ID: 280100745113
                Award Recipient :
                Funded by: The Fundamental research funds for the central Universities
                Award ID: KYZ201526
                Award Recipient :
                All the fundings of support received during this specific study: 1. A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. Grant Number: 280100745113. The URLs: http://jsycw.ec.js.edu.cn/default.aspx; 2. The Fundamental research funds for the central Universities. Grant Number: KYZ201526. b. Roles of the funder in the study: Purchasing animal and reagents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Biology and Life Sciences
                Biochemistry
                Bioenergetics
                Energy-Producing Organelles
                Mitochondria
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Energy-Producing Organelles
                Mitochondria
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Carbohydrate Metabolism
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolic Pathways
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Amino Acid Metabolism
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolites
                Biology and Life Sciences
                Genetics
                Gene Expression
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Custom metadata
                All relevant data are within the paper.

                Uncategorized

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