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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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            Author and article information

            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.

            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
            28692647 5503227 10.1371/journal.pone.0179164 PONE-D-17-06867
            © 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 : ORCID: http://orcid.org/0000-0001-6239-1711
            Funded by: The Fundamental research funds for the central Universities
            Award ID: KYZ201526
            Award Recipient : ORCID: http://orcid.org/0000-0001-6239-1711
            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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