Decorin improves human pancreatic β-cell function and regulates ECM expression in vitro

Matrix Biology, vol. 115, pp. 160–183

Abstract

Transplantation of islets of Langerhans is a promising alternative treatment strategy in severe cases of type 1 diabetes mellitus; however, the success rate is limited by the survival rate of the cells post-transplantation. Restoration of the native pancreatic niche during transplantation potentially can help to improve cell viability and function. Here, we assessed for the first time the regulatory role of the small leucine-rich proteoglycan decorin (DCN) in insulin secretion in human β-cells, and its impact on pancreatic extracellular matrix (ECM) protein expression in vitro. In depth analyses utilizing next-generation sequencing as well as Raman microspectroscopy and Raman imaging identified pathways related to glucose metabolism to be upregulated in DCN-treated cells, including oxidative phosphorylation within the mitochondria as well as proteins and lipids of the endoplasmic reticulum. We further showed the effectiveness of DCN in a transplantation setting by treating collagen type 1-encapsulated β-cell-containing pseudo-islets with DCN. Taken together, in this study, we demonstrate the potential of DCN to improve the function of insulin-secreting β-cells while reducing the expression of ECM proteins affiliated with fibrotic capsule formation, making DCN a highly promising therapeutic agent for islet transplantation.

Authors 10

1. Max Urbanczyk

   University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

2. Abiramy Jeyagaran

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

   NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany

3. Aline Zbinden Aachen Department of Immunology, Leiden University Medical Center Leiden

   Leiden University Medical Center · University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany; Department of Immunology, Leiden University Medical Center Leiden, ZA 2333, the Netherlands

   Department of Immunology, Leiden University Medical Center Leiden, ZA 2333, the Netherlands

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

4. Chuan‐en Lu

   University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

5. Julia Marzi

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany

   Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

   NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany

6. Laurence Kuhlburger

   Quantitative Biology Center · University of Tübingen

   Affiliation as printed

   Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, Tübingen, Germany; Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, Tübingen, Germany

   Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, Tübingen, Germany

   Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, Tübingen, Germany

7. Sven Nahnsen

   Quantitative Biology Center · University of Tübingen

   Affiliation as printed

   Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, Tübingen, Germany; Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, Tübingen, Germany

   Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, Tübingen, Germany

   Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, Tübingen, Germany

8. Shannon Lee Layland

   University of Tübingen

   Affiliation as printed

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany; Department of Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany

   Department of Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany

   Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

9. Garry P. Duffy

   Science Foundation Ireland · Ollscoil na Gaillimhe – University of Galway · Trinity College Dublin · Advanced Materials and BioEngineering Research

   Affiliation as printed

   Discipline of Anatomy and the Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Advanced Materials for Biomedical Engineering (AMBER), Trinity College Dublin & National University of Ireland Galway, Galway, Ireland

   Discipline of Anatomy and the Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland

   Science Foundation Ireland (SFI) Centre for Research in Advanced Materials for Biomedical Engineering (AMBER), Trinity College Dublin & National University of Ireland Galway, Galway, Ireland

10. Katja Schenke‐Layland corresponding

    Natural and Medical Sciences Institute · University of Tübingen

    Affiliation as printed

    Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany. Electronic address: katja.schenke-layland@uni-tuebingen.de

    Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany

    Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Silcherstr. 7/1, Tübingen 72076, Germany

    NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany