Cardiac fibroblast to myofibroblast differentiation in vivo and in vitro: expression of focal adhesion components in neonatal and adult rat ventricular myofibroblasts.
In fibrosing hearts, myofibroblasts are associated with cardiac extracellular matrix remodeling. Expression of key genes in the transition of cardiac fibroblast to myofibroblast phenotype in post-myocardial infarction heart and in vitro has not been well addressed. Contractile, focal adhesion-associated, receptor proteins, fibroblast growth factor-2 (FGF-2) expression, and motility were compared to assess phenotype in adult and neonatal rat cardiac fibroblasts and myofibroblasts. Neonatal and adult fibroblasts undergo phenotypic transition to myofibroblastic cells, marked by increased alpha-smooth muscle actin (alphaSMA), smooth muscle myosin heavy chain (SMemb), extra domain-A (ED-A) fibronectin, paxillin, tensin, FGF-2, and TbetaRII receptor. Elevated ED-A fibronectin confirmed fibroblast to supermature myofibroblastic phenotype transition. Presence of myofibroblasts in vivo was noted in sections of healed infarct scar after myocardial infarction, and their expression is similar to that in culture. Thus, cultured neonatal and adult cardiac fibroblasts transition to myofibroblasts in vitro and share expression profiles of cardiac myofibroblasts in vivo. Reduced motility with in vitro passage reflects enhanced production of focal adhesions.
Santiago
Jon-Jon
JJ
Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Canada.
Dangerfield
Aran L
AL
Rattan
Sunil G
SG
Bathe
Krista L
KL
Cunnington
Ryan H
RH
Raizman
Joshua E
JE
Bedosky
Kristen M
KM
Freed
Darren H
DH
Kardami
Elissavet
E
Dixon
Ian M C
IM
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D022001:Focal Adhesions / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005353:Fibronectins; D016222:Fibroblast Growth Factor 2