Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.
Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.
Chuva de Sousa Lopes
Susana M
SM
Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Feijen
Alie
A
Korving
Jeroen
J
Korchynskyi
Olexander
O
Larsson
Jonas
J
Karlsson
Stefan
S
ten Dijke
Peter
P
Lyons
Karen M
KM
Goldschmeding
Roel
R
Doevendans
Pieter
P
Mummery
Christine L
CL
D000375:Aging / Q000502:physiology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002460:Cell Line; D055513:Connective Tissue Growth Factor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology; D006321:Heart / Q000196:embryology*; D006325:Heart Atria / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009203:Myocardial Infarction / Q000209:etiology*; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C526318:CCN2 protein, mouse; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor