Universität zu Köln

Chowdhury, Arpita, Herzog, Christine, Hasselbach, Lisa, Khouzani, Houra Loghmani, Zhang, Jinli, Hammerschmidt, Matthias, Rudat, Carsten, Kispert, Andreas, Gaestel, Matthias ORCID: 0000-0002-4944-4652, Menon, Manoj B. ORCID: 0000-0001-5859-0347, Tudorache, Igor, Hilfiker-Kleiner, Denise, Muehlfeld, Christian, Schmitto, Jan Dieter, Mueller, Martin and Theilmeier, Gregor (2014). Expression of fibulin-6 in failing hearts and its role for cardiac fibroblast migration. Cardiovasc. Res., 103 (4). S. 509 - 521. OXFORD: OXFORD UNIV PRESS. ISSN 1755-3245

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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-beta 1. 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-beta 1 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-beta 1 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-beta 1 signalling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chowdhury, Arpita UNSPECIFIED UNSPECIFIED UNSPECIFIED Herzog, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasselbach, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Khouzani, Houra Loghmani UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Jinli UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudat, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Kispert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaestel, Matthias UNSPECIFIED orcid.org/0000-0002-4944-4652 UNSPECIFIED Menon, Manoj B. UNSPECIFIED orcid.org/0000-0001-5859-0347 UNSPECIFIED Tudorache, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Hilfiker-Kleiner, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehlfeld, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitto, Jan Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Theilmeier, Gregor UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-429700
DOI:	10.1093/cvr/cvu161
Journal or Publication Title:	Cardiovasc. Res.
Volume:	103
Number:	4
Page Range:	S. 509 - 521
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1755-3245
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTRACELLULAR-MATRIX; CELL-MIGRATION; MYOCARDIAL-INFARCTION; EPITHELIAL-CELLS; GENE-EXPRESSION; PROLIFERATION; HEMICENTIN; FIBROSIS; MOUSE; DIFFERENTIATION Multiple languages Cardiac & Cardiovascular Systems Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42970