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Title: TGF-beta(1)-induced cardiac myofibroblasts are nonproliferating functional cells carrying DNA damages
Authors: Petrov, Victor ×
van Pelt, Jos
Vermeesch, Joris
Van Duppen, Victor
Vekemans, Katrien
Fagard, Robert
Lijnen, Paul #
Issue Date: Apr-2008
Publisher: Elsevier inc
Series Title: Experimental Cell Research vol:314 issue:7 pages:1480-1494
Abstract: TGF-beta(1) induces differentiation and total inhibition of cardiac MyoFb cell division and DNA synthesis. These effects of TGF-beta(1) are irreversible. inhibition of MyoFb proliferation is accompanied with the expression of Smad1, Mad1, p15Ink4B and total inhibition of telomerase activity. Surprisingly, TGF-beta(1)-activated MyoFbs are growth-arrested not only at G1-phase but also at S-phase of the cell cycle. Staining with TUNEL indicates that these cells carry DNA damages. However, the absolute majority of MyoFbs are non-apoptotic cells as established with two apoptosis-specific methods, flow cytometry and caspase-dependent cleavage of cytokeratin 18. Expression in MyoFbs of proliferative cell nuclear antigen even in the absence of serum confirms that these MyoFbs perform repair of DNA damages. These results suggest that TGF-beta(1)-activated MyoFbs can be growth-arrested by two checkpoints, the G1/S checkpoint, which prevents cells from entering S-phase and the intra-S checkpoint, which is activated by encountering DNA damage during the S phase or by unrepaired damage that escapes the G1/S checkpoint. Despite carrying of the DNA damages TGF-beta(1)-activated MyoFbs are highly functional cells producing lysyl oxidase and contracting the collagen matrix. (C) 2008 Elsevier Inc. All rights reserved.
URI: 
ISSN: 0014-4827
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Abdominal Transplantation
Hematology Section (-)
Hypertension and Cardiovascular Epidemiology
Clinical Genetics Section (-)
Hepatology
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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