Diabetologie und Stoffwechsel 2018; 13(S 01): S19
DOI: 10.1055/s-0038-1641809
Poster
Typ-2-Diabetes – Pathophysiologie I
Georg Thieme Verlag KG Stuttgart · New York

TGFß regulates metabolism of human skeletal muscle cells by miRNAs

S Höckele
1   Helmholtz Zentrum München, Institute of Experimental Genetics, Neuherberg, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
,
P Huypens
1   Helmholtz Zentrum München, Institute of Experimental Genetics, Neuherberg, Germany
,
C Hoffmann
3   University Hospital Tübingen, Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Tübingen, Germany
,
T Jeske
4   Helmholtz Zentrum München, Institute of Bioinformatics and Systems Biology, Neuherberg, Germany
5   Dr. Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Department of Pediatrics, München, Germany
,
M Hastreiter
6   Helmholtz Zentrum München, Institute of Computational Biology, Neuherberg, Germany
7   Technische Universität München, Lehrstuhl für Genomorientierte Bioinformatik, Freising, Germany
,
A Böhm
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
3   University Hospital Tübingen, Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Tübingen, Germany
8   University of Tübingen, Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München, Tübingen, Germany
,
J Beckers
1   Helmholtz Zentrum München, Institute of Experimental Genetics, Neuherberg, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
9   Technische Universität München, Institute of Experimental Genetics, Freising, Germany
,
HU Häring
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
3   University Hospital Tübingen, Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Tübingen, Germany
8   University of Tübingen, Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München, Tübingen, Germany
,
M Hrabe de Angelis
1   Helmholtz Zentrum München, Institute of Experimental Genetics, Neuherberg, Germany
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
9   Technische Universität München, Institute of Experimental Genetics, Freising, Germany
,
C Weigert
2   German Center for Diabetes Research (DZD), Neuherberg, Germany
3   University Hospital Tübingen, Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Tübingen, Germany
8   University of Tübingen, Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München, Tübingen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2018 (online)

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    TGFβ plays an important role in skeletal muscle by inhibiting cell differentiation and regulating inflammation and extracellular matrix production. Recent data link TGFβ with reduced expression of mitochondrial regulators, key regulators of β-oxidation, and negative influence on insulin response, providing a potential mechanism for exercise non-response.

    To investigate the (post)transcriptional mechanisms of this TGFβ-dependent regulation and to identify epigenetic markers of exercise non-response we performed long and small RNA sequencing of primary human skeletal muscle cells stimulated with TGFβ1 before 5 d of differentiation. Sequencing data were analyzed bioinformatically using an annotation-based pipeline and USB (unique sequence based) analysis for sncRNAs.

    Pathway and regulator enrichment analyses revealed downregulation of several transcripts of mitochondrial genes including all mitochondrially encoded subunits of complex I and IV after TGFβ1 stimulation. There was a decrease of transcripts of regulators of metabolic pathways, and of muscle cell differentiation while transcripts of extracellular matrix proteins were increased in TGFβ1 stimulated cells. Part of the data was confirmed on protein level using immunoblot analyses. Analysis of sncRNA sequencing data showed upregulation of miR-143 and miR-31 after TGFβ1 stimulation, and downregulation of miR-206, miR-133b, miR-499, and miR-208b. These results were confirmed by qPCR. A clustered set of sncRNAs is predicted to target within the mitochondrial genome.

    Functional relevance of interesting sncRNAs will be validated in skeletal muscle cell experiments. Finally, we plan to investigate experimentally confirmed candidates in human muscle biopsy samples of individuals with a different response to exercise intervention.


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