Arpita Chowdhury1, Christine Herzog1, Lisa Hasselbach1, Houra Loghmani Khouzani1, Jinli Zhang2, Matthias Hammerschmidt2, Carsten Rudat3, Andreas Kispert3, Matthias Gaestel4, Manoj B Menon4, Igor Tudorache5, Denise Hilfiker-Kleiner6, Christian Mühlfeld7, Jan Dieter Schmitto5, Martin Müller1, Gregor Theilmeier8. 1. Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany. 2. Institute of Developmental Biology, Cologne University, Cologne, Germany. 3. Institute for Molecular Biology, Hannover Medical School, Hannover, Germany. 4. Institute of Physiological Chemistry, Hannover Medical School, Hannover, Germany. 5. Department of Cardio-Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. 6. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. 7. Institute of Applied Anatomy, Hannover Medical School, Hannover, Germany. 8. Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany theilmeier.gregor@mh-hannover.de.
Abstract
AIMS: The cardiac extracellular matrix (ECM) undergoes a dynamic transition following myocardial infarction. Fibulin-6 is expressed in cell junctions particularly in tissues subjected to significant mechanical stress. Fibulin-6 deficiency results in defective cell migration in nematodes and early embryonic lethality in mice. The role of fibulin-6 in healthy and failing myocardium is unknown. We have examined the expression and distribution pattern of fibulin-6 during myocardial remodelling (MR) and detailed its effect on the migratory function of cardiac fibroblasts (CFs) in response to TGF-β1. METHODS AND RESULTS: In healthy murine myocardium, fibulin-6 expression is largely confined to larger coronary arteries. It is induced during the early and the late phase of remodelling after infarction in murine hearts predominantly in the scar-muscle junction. Similar results are obtained in human ischaemic cardiomyopathy. Fibulin-6 is mostly expressed in close vicinity to vimentin-positive cells and is also abundantly expressed in vitro in cultured neonatal CF. TGF-β1 does not induce smooth muscle actin in fibroblasts deficient of fibulin-6, which also compromised their migration. Cells that had migrated expressed more fibulin-6 compared with stationary cells. Plated on fibulin-6-depleted matrix, stress fibre induction in fibroblast in response to TGF-β1 was impaired. In ex vivo explant cultures from post-infarct myocardium, the number of emigrating fibroblasts was also significantly reduced by fibulin-6 siRNA knockdown. CONCLUSION: Fibulin-6, a fibroblast-released ECM protein, may play an important role during MR by imparting an effect on CF migration in close and complementary interplay with TGF-β1 signalling. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The cardiac extracellular matrix (ECM) undergoes a dynamic transition following myocardial infarction. Fibulin-6 is expressed in cell junctions particularly in tissues subjected to significant mechanical stress. Fibulin-6 deficiency results in defective cell migration in nematodes and early embryonic lethality in mice. The role of fibulin-6 in healthy and failing myocardium is unknown. We have examined the expression and distribution pattern of fibulin-6 during myocardial remodelling (MR) and detailed its effect on the migratory function of cardiac fibroblasts (CFs) in response to TGF-β1. METHODS AND RESULTS: In healthy murine myocardium, fibulin-6 expression is largely confined to larger coronary arteries. It is induced during the early and the late phase of remodelling after infarction in murine hearts predominantly in the scar-muscle junction. Similar results are obtained in humanischaemic cardiomyopathy. Fibulin-6 is mostly expressed in close vicinity to vimentin-positive cells and is also abundantly expressed in vitro in cultured neonatal CF. TGF-β1 does not induce smooth muscle actin in fibroblasts deficient of fibulin-6, which also compromised their migration. Cells that had migrated expressed more fibulin-6 compared with stationary cells. Plated on fibulin-6-depleted matrix, stress fibre induction in fibroblast in response to TGF-β1 was impaired. In ex vivo explant cultures from post-infarct myocardium, the number of emigrating fibroblasts was also significantly reduced by fibulin-6 siRNA knockdown. CONCLUSION:Fibulin-6, a fibroblast-released ECM protein, may play an important role during MR by imparting an effect on CF migration in close and complementary interplay with TGF-β1 signalling. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Meei-Hua Lin; Bill D Pope; Takako Sasaki; Daniel P Keeley; David R Sherwood; Jeffrey H Miner Journal: Dev Dyn Date: 2020-02-12 Impact factor: 3.780
Authors: Benjamin L King; Michael C Rosenstein; Ashley M Smith; Christina A Dykeman; Grace A Smith; Viravuth P Yin Journal: NPJ Regen Med Date: 2018-05-29
Authors: Arpita Chowdhury; Abhishek Aich; Gaurav Jain; Katharina Wozny; Christian Lüchtenborg; Magnus Hartmann; Olaf Bernhard; Martina Balleiniger; Ezzaldin Ahmed Alfar; Anke Zieseniss; Karl Toischer; Kaomei Guan; Silvio O Rizzoli; Britta Brügger; Andrè Fischer; Dörthe M Katschinski; Peter Rehling; Jan Dudek Journal: Cell Rep Date: 2018-10-16 Impact factor: 9.423